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UHS NHS FT Electronic Data Management System Access for External Monitors and Regulators for Research for email
Description
Department of Research and Development University Hospital Southampton NHS Foundation Trust C Level West Wing, Mailpoint 218 Southampton SO16 6YD PLEASE ADDRESS ALL EDMS ACCESS
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/Media/Southampton-Clinical-Research/BRC-CRF-templates/UHS-NHS-FT-Electronic-Data-Management-System-Access-for-External-Monitors-and-Regulators-for-Research-for-email.pdf
DVd_Twice weekly_Daratumumab-Bortezomib-Dexamethasone_Cycles 1 to 8
Description
Chemotherapy Protocol Myeloma DVd (twice weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) Regimen • Myeloma – Bortezomib (twice weekly)-Daratumumab-Dexamethasone Indication • Daratumumab in combination with bortezomib and dexamethasone is recommended for use within the Cancer Drugs Fund as an option for treating relapsed multiple myeloma in people who have had 1 previous treatment. • A weekly bortezomib regimen is available for patients who experience neuropathy or those with pre-existing neuropathy. Note both regimens include 32 doses of bortezomib; therefore bortezomib continues to the end of cycle 10 in the weekly regimen. Ensure the correct regimen is selected. Toxicity Drug Bortezomib Daratumumab Dexamethasone Adverse Effect GI disturbances, peripheral neuropathy, hypotension, dizziness, blurred vision, headache, musculoskeletal pain, pyrexia Infusion related reactions, hypotension, headache, rash, urticaria, pruritus, nausea, vomiting, respiratory tract infections (including pneumonia), neutropenia, thrombocytopenia, anaemia, lymphopenia, peripheral neuropathy, diarrhoea, muscle spasms, fatigue, pyrexia and peripheral oedema, blood transfusion related events Weight gain, gastrointestinal disturbances, hyperglycaemia, CNS disturbances, Cushingoid changes, glucose intolerance. The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Monitoring Drugs • FBC, U&Es, Ca2+ and LFTs prior to day one of each cycle of treatment. • Paraprotein and / or light chains prior to each cycle. • All patients should be tested for hepatitis B virus (HBV) before initiating treatment with daratumumab. Those patients who test positive for HBV infection should be discussed with a consultant specialising in HBV prior to initiating treatment with daratumumab to plan monitoring requirements whilst on treatment. Patients may also be tested for hepatitis C, CMV and HIV at the same time if clinically appropriate. Version 1(July 2019) Page 1 of 16 Myeloma –DVd (twice weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) • Send a blood sample to transfusion and inform patient and transfusion laboratory that patient is due to commence daratumumab. Patient will require red cell phenotyping as cross match fails due to binding of daratumumab to red cells. • Regular monitoring of blood glucose is considered good practice due to dexamethasone use. Dose Modifications The dose modifications listed are for haematological, liver and renal function and drug specific toxicities only. Dose adjustments may be necessary for other toxicities as well. In principle all dose reductions due to adverse drug reactions should not be re-escalated in subsequent cycles without consultant approval. It is also a general rule for chemotherapy that if a third dose reduction is necessary treatment should be stopped. Please discuss all dose reductions / delays with the relevant consultant before prescribing, if appropriate. The approach may be different depending on the clinical circumstances. Haematological No dose reductions of daratumumab are recommended. Dose delay may be required to allow recovery of blood cell counts in the event of haematological toxicity. Always refer to the responsible consultant, as any dose delays will be dependent on clinical circumstances and treatment intent. Low counts can be a consequence of bone marrow infiltration as well as drug toxicity. Consider blood transfusion or the use of erythropoietin according to NICE TA323 if patient symptomatic of anaemia or where the haemoglobin is less than 8g/dL (80g/L). Consider growth factor support as an alternative to the options below, particularly where there is evidence of bone marrow suppression. To initiate a new cycle of daratumumab, the neutrophil count should be 1x109/L or greater and the platelet count should be 50x109/L or greater, unless the low counts are due to bone marrow infiltration with myeloma. In this situation the daratumumab may be administered at the discretion of the treating consultant haematologist with the appropriate blood product and growth factor support. Version 1(July 2019) Page 2 of 16 Myeloma –DVd (twice weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) Neutrophils (x109/L) Dose Modifications (Daratumumab and Bortezomib) Less than 0.5x109/L or febrile neutropenia (fever greater than or equal to 38.5°C and neutrophils less than 1) Interrupt daratumumab treatment and monitor FBC weekly. Once neutrophils recover to 1x109/L, resume daratumumab at a dose of 16mg/kg. Bortezomib - Consider treatment delay or dose reduction or growth factor support. Seek consultant advice. Platelets (x109/L) Dose Modifications Daratumumab Less than 50x109/L Interrupt daratumumab treatment and monitor FBC weekly. Once platelets recover to 50x109/L or greater resume daratumumab at a dose of 16mg/kg. Bortezomib Less than 25x109/L Consider treatment delay or dose reduction or platelet transfusion. Seek consultant advice. Hepatic Impairment Please note that the approach may be different where abnormal liver function tests are due to disease involvement. Drug Bortezomib Daratumumab Bilirubin µmol/L AST/ALT units/L Dose (% of original dose) 1.5xULN or below greater than 1.5xULN N/A 100% Initiate treatment at 0.7mg/m2. The dose may be escalated to N/A 1mg/m2 or reduced to 0.5mg/m2 in subsequent cycles based on patient tolerability. No formal studies of daratumumab in patients with hepatic impairment have been conducted. Based on population pharmacokinetic analysis no dosage adjustments are necessary for patients with hepatic impairment Renal Impairment Drug Bortezomib Creatinine Clearance (ml/min) greater than 20 Dose (% of original dose) 100% 20 and below Clinical decision Daratumumab No adjustments necessary Other Dose reductions or interruptions in therapy are not necessary for those toxicities that are considered unlikely to be serious or life threatening. For example, alopecia, altered taste or nail changes Version 1(July 2019) Page 3 of 16 Myeloma –DVd (twice weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) Bortezomib For patients experiencing NCI-CTC grade 1 neuropathy without loss of function or pain continue with full dose bortezomib. For NCI-CTC grade 1 with pain or grade 2 neuropathy reduce the dose of bortezomib to 1mg/m2. For NCI-CTC grade 2 with pain or grade 3 neuropathy discontinue treatment until symptoms have resolved to NCI-CTC grade 1 or less then reinitiate bortezomib at a dose of 0.7mg/m2 For NCI-CTC grade 4 neuropathy and/or severe autonomic neuropathy discontinue bortezomib. For any other NCI-CTC grade 3 non haematological toxicity bortezomib should be discontinued until symptoms have resolve to NCI-CTC grade 1 or below. On the first occurrence treatment may be reinitiated at a dose of 1mg/m2. Following second occurrence to dose should be further reduced to 0.7mg/m2 once symptoms have resolved. If the toxicity is not resolved or if it recurs at the lowest dose, discontinuation of bortezomib must be considered unless the benefit of treatment clearly outweighs the risk. Dexamethasone For patients who are elderly or unable to tolerate the standard dose of dexamethasone the dose given the day after bortezomib alone (days 5, 9 and 12 from cycle 4 onwards) may be reduced. Please note the doses before and the day after each daratumumab are to reduce the risk of infusion related reactions and as a steroid component of the triple combination. Infusion related reactions (IRR) Infusion reactions are reported in approximately half of patients who receive daratumumab and may occur up to 48 hours after the infusion has finished. The majority of infusion related reactions, 46%, occur with the first infusion, 2% with the second infusion and 3% with subsequent infusions. Signs and symptoms include bronchospasm, hypoxia, dyspnoea, hypertension, respiratory symptoms such as cough, wheezing, larynx and throat tightness and irritation, laryngeal oedema, pulmonary oedema, nasal congestion and allergic rhinitis. For infusion reactions of any grade/severity, immediately interrupt the infusion and manage the symptoms. Management of infusion reactions may further require reduction in the rate of infusion, or treatment discontinuation as outlined below. Version 1(July 2019) Page 4 of 16 Myeloma –DVd (twice weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) IRR grade Grade 1-2 (mild to moderate) Grade 3 (severe) Grade 4 (life threatening) Dose modification Once symptoms resolve, resume the infusion at no more than half the rate at which the reaction occurred. If the patient does not experience any further reaction symptoms, infusion rate escalation may resume at increments and intervals as appropriate. If the intensity of the reaction decreases to ≤Grade 2, consider restarting the infusion at no more than half the rate at which the reaction occurred. If the patient does not experience additional symptoms, resume infusion rate escalation at increments and intervals as appropriate. Permanently discontinue treatment upon the third occurrence of a Grade 3 or greater reaction. Permanently discontinue treatment. Version 1(July 2019) Page 5 of 16 Myeloma –DVd (twice weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) Regimen 21 day cycle. Continue daratumumab until disease progression. Note that cycle length changes to 28 days from cycle 9 onwards. Cycles 1 to 3 Drug Bortezomib Daratumumab Dose 1.3mg/m2 16mg/kg 20mg once a day Dexamethasone (iv dose equivalent) Dexamethasone 20mg once a day Dexamethasone 4mg once a day Days 1, 4, 8,11 1,8,15 1, 8, 15 2, 4, 5, 9, 11, 12 16, 17 Administration Subcutaneous Intravenous infusion in 500ml sodium chloride 0.9% IV bolus Can be given as 20mg orally from second infusion onwards. Reduce dose to 10mg orally (or iv dose equivalent) in over 75yrs Oral Reduce dose to 10mg in over 75yrs Post daratumumab infusion to reduce the risk of delayed infusion reactions Cycles 4 to 8 Drug Bortezomib Daratumumab Dexamethasone Dexamethasone Dose 1.3mg/m2 16mg/kg 20mg once a day 20mg once a day Days 1, 4, 8, 11 1 1 2, 4, 5, 8, 9, 11, 12 Administration Subcutaneous Intravenous infusion in 500ml sodium chloride 0.9% Orally Can be given as 20mg intravenous equivalent. Reduce dose to 10mg orally (or iv dose equivalent) in over 75yrs Oral Reduce dose to 10mg in over 75yrs Cycles 9 onwards – see separate protocol Dose Information • Daratumumab will be prescribed in accordance with the national dose bands (20 NS). • Bortezomib dose will be dose banded in accordance with the national dose bands (2.5). Version 1(July 2019) Page 6 of 16 Myeloma –DVd (twice weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) • Dexamethasone is available as 4mg, 2mg and 500microgram tablets and 3.3mg in 1ml injection (equivalent to 4mg orally) Administration Information • The rate of daratumumab administration varies and depends on infusion related reactions. In order to determine the rate of the second and ongoing infusions all reactions and the first reaction free infusion must be recorded in the ARIA journal. • Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an in-line, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC, PP or PE administration sets must be used. First infusion Second infusionb Subsequent infusionsc Final volume 500ml 500ml 500ml Initial rate (first hour) 25ml/hour 50ml/hour 100ml/hour Rate incrementa 25ml/hour every hour 50ml/hour every hour 50ml/hour every hour Maximum rate 100ml/hour 200ml/hour 200ml/hour a Consider the incremental escalation of the infusion rate only in the absence of infusion reactions with the previous infusion b Escalate only if the patient’s first infusion of daratumumab was well tolerated (defined by an absence of NCI-CTC grade 2 or greater infusion-related reactions during the first 3 hours). If the previous infusion was not well tolerated then instructions for the first infusion c Escalate only if the patient’s first 2 infusions of daratumumab were well tolerated (defined by an absence of NCI-CTC grade 1 or greater infusion-related reactions during a final infusion rate of greater than or equal to 100 ml/hr). If the previous infusion was not well tolerated, then instructions for the second infusion will be used. For guidance on infusion rates in the case of infusion related reactions. See the managing infusion reactions section above. Rapid Infusion Protocol Data from a prospective, single-center and open label safety study of an accelerated daratumumab infusion suggests that a rapid (90 minute) daratumumab infusion schedule is well tolerated and safe, when administered from the 3rd infusion onwards in patients who have tolerated the 500mL daratumumab infusion at the manufacturer recommended rates. The rapid rate of infusion is currently unlicensed. Inclusion criteria for daratumumab rapid rate infusion • Patients from third daratumumab infusion onwards who have received and tolerated the previous daratumumab 100mL/hour initial infusion rate with escalation to the standard manufacturer licensed rate without Grade 1 infusion related reactions. • Patients who have given consent to rapid rate daratumumab infusion if required by the individual Trust Version 1(July 2019) Page 7 of 16 Myeloma –DVd (twice weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) Exclusion criteria for daratumumab rapid rate infusion • Previous greater than or equal to grade 3 infusion related toxicity with daratumumab • Infusion related reactions greater than or equal to grade 1 with the most recent daratumumab infusion given at the standard manufacturer licensed rate. • Cardiac amyloid patients • Patients receiving daratumumab as part of clinical trials (follow trial protocol) Rapid infusion rate Daratumumab prepared in 500mL sodium chloride 0.9% • Infuse 100mL of the daratumumab infusion (20%) of the dose over 30 minutes • Then infuse the remaining 400mL (80% of the dose) over 60 minutes (total infusion time 90 minutes). Monitoring • Check vital signs before the start of the infusion, every 15 minutes during the first 60 minutes of the infusion and at the end of the infusion for all daratumumab infusions. • Monitor patient for adverse effects. For the first rapid rate infusion, observe patients in the Day Unit for 30 minutes after infusion completion to assess for delayed infusion related reactions. • Closer monitoring is required if the patient has a history of uncontrolled hypertension, pre-existing COPD, asthma or other respiratory comorbidities. These patients should be discussed with the consultant. Additional therapy • Consider allopurinol 300mg once a day for seven days for the first cycle only oral • No anti-emetics are required • Premedication required 1 to 3 hours before every daratumumab infusion: - dexamethasone – see regimen for dose details - chlorphenamine 10mg intravenous - paracetamol 1000mg oral - montelukast 10mg oral for the first two cycles only and the first “fast infusion” if this does not occur on cycle two • Consider anti-infective prophylaxis including: - aciclovir 400mg twice a day oral - co-trimoxazole 960mg once a day oral on Monday, Wednesday and Friday only - fluconazole 100mg once a day oral if recurrent oral candidiasis • Bisphosphonates in accordance with local policies. • Mouthwashes according to local or national policy on the treatment of mucositis. • Gastric protection with a proton pump inhibitor or an H2 antagonist may be considered in patients considered at high risk of GI ulceration or bleed. Version 1(July 2019) Page 8 of 16 Myeloma –DVd (twice weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) • As required for the treatment of infusion related reactions for patients at high risk of respiratory complications: - sodium chloride 0.9% 500ml intravenous - salbutamol 2.5mg nebulised - hydrocortisone sodium succinate 100mg intravenous - chlorphenamine 10mg intravenous - paracetamol 1000mg oral - oxygen as required Additional Information • All instances of infusion related reaction must be recorded on ARIA. Daratumumab will continue to be administered at the cycle one rate until a reaction free infusion is noted. • Daratumumab interferes with indirect antiglobulin tests as it binds to CD38 on red blood corpuscles (RBCs) and interferes with compatibility testing, including antibody screening and cross matching. Daratumumab interference mitigation methods include treating reagent RBCs with dithiothreitol (DTT) to disrupt daratumumab binding or other locally validated methods. Since the Kell blood group system is also sensitive to DTT treatment, Kell-negative units should be supplied after ruling out or identifying alloantibodies using DTT-treated RBCs. Alternatively, phenotyping or genotyping may also be considered. • Daratumumab may be detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for monitoring disease monoclonal immunoglobulins (M protein). This can lead to false positive SPE and IFE assay results for patients with IgG kappa myeloma protein impacting initial assessment of complete responses by International Myeloma Working Group (IMWG) criteria. In patients with persistent very good partial response, consider other methods to evaluate the depth of response. Coding • Procurement –X70.8 • Delivery – X72.9, X72.4 References 1. Janssen-Cilag Limited (18 Dec 2018). Darzalex 20mg/ml Summary of Product Characteristics. Electronic Medicines Compendium. Online at https://www.medicines.org.uk/emc/product/7250 , accessed 01 July 2019. 2. National Institute for Health and Care Excellence (2019). Daratumumab with bortezomib and dexamethasone for previously treated multiple myeloma. [TA573]. London: National Institute for Health and Care Excellence. 3. Thames Valley Strategic Cancer Network Myeloma Group MM47 DaraVelDex Protocol version 2.0 April 2019. 4. 90 minute daratumumab infusion is safe in multiple myeloma. Leukemia. Hallie Barr et al. Accessed 27/11/18 https://doi.org/10.1038/s41375-018-0120-2. Version 1(July 2019) Page 9 of 16 Myeloma –DVd (twice weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) REGIMEN SUMMARY Myeloma DVd (twice weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) Cycle 1 Days 1 and 8 1. Warning – Inform blood transfusion Administration Instructions Daratumumab interferes with indirect antiglobulin tests as it binds to CD38 on red blood corpuscles (RBCs) and interferes with compatibility testing, including antibody screening and cross matching. Daratumumab interference mitigation methods include treating reagent RBCs with dithiothreitol (DTT) to disrupt daratumumab binding or other locally validated methods. Since the Kell blood group system is also sensitive to DTT treatment, Kell-negative units should be supplied after ruling out or identifying alloantibodies using DTT-treated RBCs. Alternatively, phenotyping or genotyping may also be considered. Daratumumab may be detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for monitoring disease monoclonal immunoglobulins (M protein). This can lead to false positive SPE and IFE assay results for patients with IgG kappa myeloma protein impacting initial assessment of complete responses by International Myeloma Working Group (IMWG) criteria. In patients with persistent very good partial response, consider other methods to evaluate the depth of response Please inform blood transfusion when a patient is prescribed daratumumab 2. Chlorphenamine 10mg intravenous 3. Dexamethasone 20mg intravenous equivalent Administration Instructions Administer 20mg intravenous equivalent – Can be administered as 20mg orally from second infusion onwards. Reduce dose to 10mg intravenous equivalent or 10mg orally in patients over 75 years old. 4. Paracetamol 1000mg oral Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 5. Montelukast 10mg oral 6. Daratumumab 16mg/kg in 500ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of daratumumab administration varies and is dependant the occurance and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC, PP or PE administration sets must be used. 7. Bortezomib 1.3mg/m2 subcutaneous injection 8. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 9. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 10. Paracetamol 1000mg oral when required for the relief of infusion related reactions 11. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions 12. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Version 1(July 2019) Page 10 of 16 Myeloma –DVd (twice weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) Cycle 1 Days 4 and 11 13. Bortezomib 1.3mg/m2 subcutaneous injection Cycle 1 Day 15 14. Chlorphenamine 10mg intravenous 15. Dexamethasone 20mg intravenous equivalent Administration Instructions Administer 20mg intravenous equivalent – Can be administered as 20mg orally from second infusion onwards. Reduce dose to 10mg intravenous equivalent or 10mg orally in patients over 75 years old. 16. Paracetamol 1000mg oral Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 17. Montelukast 10mg oral 18. Daratumumab 16mg/kg in 500ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of daratumumab administration varies and is dependant the occurance and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC, PP or PE administration sets must be used. 19. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 20. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 21. Paracetamol 1000mg oral when required for the relief of infusion related reactions 22. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions 23. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Cycle 1 Take home medicines (day 1 only) 24. Dexamethasone 20mg on days 2, 4, 5, 9, 11 and 12 oral Administration Information Reduce dose to 10mg in patients over 75 years old Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice. 25. Dexamethasone 4mg on days 16 and 17 oral Administration Information Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice 26. Allopurinol 300mg once a day for 7 days oral Administration information Take in the morning with food and plenty of water. This should be supplied for the first cycle only. 27. Aciclovir 400mg twice a day for 21 days oral Administration Instructions Please supply 21 days or an original pack if appropriate. Version 1(July 2019) Page 11 of 16 Myeloma –DVd (twice weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) 28. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 21 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 21 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice. 29. Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - esomeprazole 20mg once a day oral - omeprazole 20mg once a day oral - lansoprazole 15mg once a day oral - pantoprazole 20mg once a day oral - rabeprazole 20mg once a day oral - cimetidine 400mg twice a day oral - famotidine 20mg once a day oral - nizatidine 150mg twice a day oral - ranitidine 150mg twice a day oral Please supply 21 days or the nearest original pack size. Cycles 2 and 3 days 1 and 8 30. Chlorphenamine 10mg intravenous 31. Dexamethasone 20mg intravenous equivalent Administration Instructions Administer 20mg intravenous equivalent – Can be administered as 20mg orally from second infusion onwards. Reduce dose to 10mg intravenous equivalent or 10mg orally in patients over 75 years old. 32. Paracetamol 1000mg oral Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 33. Montelukast 10mg oral Administration Instructions Administer during the first two cycles (six infusions). Also administer before the first ‘fast infusion’ if this occurs after cycle 2. 34. Daratumumab 16mg/kg in 500ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of daratumumab administration varies and is dependant the occurance and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC, PP or PE administration sets must be used. 35. Bortezomib 1.3mg/m2 subcutaneous injection 36. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 37. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 38. Paracetamol 1000mg oral when required for the relief of infusion related reactions 39. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions Version 1(July 2019) Page 12 of 16 Myeloma –DVd (twice weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) 40. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Cycles 2 and 3 Days 4 and 11 41. Bortezomib 1.3mg/m2 subcutaneous injection Cycles 2 and 3 Day 15 42. Chlorphenamine 10mg intravenous 43. Dexamethasone 20mg intravenous equivalent Administration Instructions Administer 20mg intravenous equivalent – Can be administered as 20mg orally from second infusion onwards. Reduce dose to 10mg intravenous equivalent or 10mg orally in patients over 75 years old. 44. Paracetamol 1000mg oral Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 45. Montelukast 10mg oral Administration Instructions Administer before the first ‘fast infusion’, this may not have occurred in cycle 2. 46. Daratumumab 16mg/kg in 500ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of daratumumab administration varies and is dependant the occurance and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC, PP or PE administration sets must be used. 47. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 48. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 49. Paracetamol 1000mg oral when required for the relief of infusion related reactions 50. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions 51. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Cycles 2 and 3 Take home medicines (day 1 only) 52. Dexamethasone 20mg on days 2, 4, 5, 9, 11 and 12 oral Administration Information Reduce dose to 10mg in patients over 75 years old Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice. 53. Dexamethasone 4mg on days 16 and 17 oral Administration Information Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice Version 1(July 2019) Page 13 of 16 Myeloma –DVd (twice weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) 54. Aciclovir 400mg twice a day for 21 days oral Administration Instructions Please supply 21 days or an original pack if appropriate. 55. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 21 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 21 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice. 56. Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - esomeprazole 20mg once a day oral - omeprazole 20mg once a day oral - lansoprazole 15mg once a day oral - pantoprazole 20mg once a day oral - rabeprazole 20mg once a day oral - cimetidine 400mg twice a day oral - famotidine 20mg once a day oral - nizatidine 150mg twice a day oral - ranitidine 150mg twice a day oral Please supply 21 days or the nearest original pack size. Cycles 4 to 8 day 1 57. Chlorphenamine 10mg intravenous 58. Dexamethasone 20mg orally Administration Instructions Administer 20mg orally. Can be administered as 20mg intravenous equivalent. Reduce dose to 10mg intravenous equivalent or 10mg orally in patients over 75 years old.. 59. Paracetamol 1000mg oral Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 60. Daratumumab 16mg/kg in 500ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of daratumumab administration varies and is dependant the occurance and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC, PP or PE administration sets must be used. 61. Bortezomib 1.3mg/m2 subcutaneous injection 62. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 63. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 64. Paracetamol 1000mg oral when required for the relief of infusion related reactions 65. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions 66. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Version 1(July 2019) Page 14 of 16 Myeloma –DVd (twice weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) Cycles 4 to 8 days 4, 8 and 11 67. Bortezomib 1.3mg/m2 subcutaneous injection Cycles 4 to 8 Take home medicines (day 1 only) 68. Dexamethasone 20mg on days 2, 4, 5, 8, 9, 11 and 12 oral Administration Information Reduce dose to 10mg in patients over 75 years old Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice. 69. Aciclovir 400mg twice a day for 21 days oral Administration Instructions Please supply 21 days or an original pack if appropriate. 70. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 21 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 21 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice. 71. Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - esomeprazole 20mg once a day oral - omeprazole 20mg once a day oral - lansoprazole 15mg once a day oral - pantoprazole 20mg once a day oral - rabeprazole 20mg once a day oral - cimetidine 400mg twice a day oral - famotidine 20mg once a day oral - nizatidine 150mg twice a day oral - ranitidine 150mg twice a day oral Please supply 21 days or the nearest original pack size. Version 1(July 2019) Page 15 of 16 Myeloma –DVd (twice weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) DOCUMENT CONTROL Version Date Amendment Written By Approved By 1 July 2019 None Harriet Launders Pharmacist Dr Deborah Wright Pharmacist Dr Mathew Jenner Consultant Haematologist This chemotherapy protocol has been developed as part of the chemotherapy electronic prescribing project. This was and remains a collaborative project that originated from the former CSCCN. These documents have been approved on behalf of the following Trusts; Hampshire Hospitals NHS Foundation Trust NHS Isle of Wight Portsmouth Hospitals NHS Trust Salisbury NHS Foundation Trust University Hospital Southampton NHS Foundation Trust Western Sussex Hospitals NHS Foundation Trust All actions have been taken to ensure these protocols are correct. However, no responsibility can be taken for errors that occur as a result of following these guidelines. These protocols should be used in conjunction with other references such as the Summary of Product Characteristics and relevant published papers. Version 1(July 2019) Page 16 of 16 Myeloma –DVd (twice weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8)
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Isatuximab VRD weekly
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Chemotherapy Protocol Myeloma Isa-VRD weekly Isatuximab-Lenalidomide-Bortezomib-Dexamethasone (20) Regimen Myeloma – Isa-VRD weekly Isatuximab-Lenalidomide-Bortezomib-Dexamethasone (20) Indication • Isatuximab in combination with Lenalidomide, Bortezomib, and Dexamethasone is recommended for use within the Cancer Drugs Fund as an option for treating untreated multiple myeloma patients who are ineligible for an autologous stem cell transplant or the patient commenced induction therapy with the combination of daratumumab plus bortezomib, thalidomide and dexamethasone with the intention of proceeding to a stem cell transplant but despite responding to such treatment the patient is now ineligible for transplantation. • Patients who have not responded to induction therapy with daratumumab plus bortezomib, thalidomide and dexamethasone are not allowed to switch to the isatuximab combination regimen outlined above. • Isatuximab will only be given in combination with bortezomib, lenalidomide and dexamethasone and that it is not to be used in combination with any other agents. • The patient is of ECOG performance status 0, 1 or 2. • Cancer Drug Fund approval – BLUETEQ is required prior to treatment. Version 1 (October 2025) Page 1 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide Toxicity Drug Adverse Effect Infusion related reactions: dyspnoea, hypertension and bronchospasm. Diarrhoea, nausea, vomiting, upper respiratory tract infections, pneumonia, neutropenia, weight decrease. Isatuximab Isatuximab interferes with indirect antiglobulin tests as it binds to CD38 on red blood corpuscles (RBCs) and interferes with compatibility testing, including antibody screening and cross matching. Isatuximab interference mitigation methods include treating reagent RBCs with dithiothreitol (DTT) to disrupt isatuximab binding or other locally validated methods. Since the Kell blood group system is also sensitive to DTT treatment, Kellnegative units should be supplied after ruling out or identifying allo-antibodies using DTT-treated RBCs. Alternatively, phenotyping or genotyping may also be considered. Isatuximab may be detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for monitoring disease monoclonal immunoglobulins (M protein). This can lead to false positive SPE and IFE assay results for patients with IgG kappa myeloma protein impacting initial assessment of complete responses by International Myeloma Working Group (IMWG) criteria. In patients with persistent very good partial response, consider other methods to evaluate the depth of response Lenalidomide Bortezomib Dexamethasone Please inform blood transfusion when a patient is prescribed isatuximab – before first administration in cycle 1. Peripheral neuropathy, pneumonia, infections, venous thrombotic events, respiratory dysfunction, rashes, hypokalaemia, hypomagnesaemia, hypocalcaemia, teratogenic risk, GI disturbances, flu-like symptoms. GI disturbances, peripheral neuropathy, hypotension, dizziness, blurred vision, headache, musculoskeletal pain, pyrexia Weight gain, gastrointestinal disturbances, hyperglycaemia, CNS disturbances, cushingoid changes, glucose intolerance. The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics and EAMS treatment protocol for full details. Monitoring Bloods • FBC at baseline. Thereafter monitor prior to each cycle. • U&Es, Ca2+ and LFTs prior to day one of each cycle of treatment. • Paraprotein and/or light chains prior to each cycle. Version 1 (October 2025) Page 2 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide • Send a blood sample to transfusion and inform patient and transfusion laboratory that patient is due to commence Isatuximab. Patient will require red cell phenotyping as cross match fails due to binding of Isatuximab to CD38 on red blood cells. • For all women of childbearing potential a negative pregnancy test must be obtained within the 3 days prior to starting lenalidomide. The test must be repeated every 4 weeks (every 2 weeks in women with irregular menstrual cycles) with the final test 4 weeks after the last dose of lenalidomide. • Virology screening before initiating treatment. • Perform a venous thromboembolism (VTE) risk assessment prior to starting treatment. Prescribe thromboprophylaxis. • Regular monitoring of blood glucose is considered good practice due to use of steroids. Dose Modifications The dose modifications listed are for haematological, liver and renal function and drug specific toxicities only. Dose adjustments may be necessary for other toxicities as well. In principle all dose reductions due to adverse drug reactions should not be re-escalated in subsequent cycles without consultant approval. It is also a general rule for chemotherapy that if a third dose reduction is necessary treatment should be stopped. Please discuss all dose reductions / delays with the relevant consultant before prescribing, if appropriate. The approach may be different depending on the clinical circumstances. Haematological Dose modifications for haematological toxicity in the table below are for general guidance only. Always refer to the responsible consultant as any dose reductions or delays will be dependent on clinical circumstances and treatment intent. Low counts can be a consequence of bone marrow infiltration as well as drug toxicity. In the event of febrile neutropenia and/or neutropenic infection, Isatuximab should be delayed or omitted until recovery. Version 1 (October 2025) Page 3 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide Dose Modifications ISATUXIMAB Neutrophils (x109/L) Dose Modifications Fall to less than 1.0 Delay or omit and resume when return to 1.0 or greater Platelets (x109/L) Dose Modifications Fall to less than 50 Delay or omit and resume when return to 50 or greater The use of colony-stimulating factors (e.g. G-CSF) should be considered to mitigate the risk of neutropenia. LENALIDOMIDE Neutrophils (x109/L) Dose Modifications Fall to less than 0.5 First Occurrence Neutropenia Interrupt lenalidomide and resume at starting dose when return to 1.0 or greater Other haematological toxicities Interrupt lenalidomide and resume at starting dose when return to 0.5 or greater. Subsequent Occurrence Fall to less than 0.5 Interrupt lenalidomide and resume at starting dose when return to 0.5 or greater. Platelets (x109/L) Dose Modifications Fall to less than 30 Interrupt lenalidomide and resume at next lower dose when return to 50 or greater. The use of colony-stimulating factors (e.g. G-CSF) should be considered to mitigate the risk of neutropenia. Dose Reduction Steps Lenalidomide Starting Dose 15 mg Dose Level -1 10 mg Dose Level -2 5 mg Dose Level -3 2.5 mg Version 1 (October 2025) Page 4 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide BORTEZOMIB Neutrophils (x109/L) Fall to less than 0.5 Platelets (x109/L) Fall to less than 25 Dose Modifications Interrupt bortezomib Dose Modifications Interrupt bortezomib Hepatic Impairment Drug Bilirubin μmol/L Isatuximab N/A Lenalidomide N/A Bortezomib > 1.5 x ULN AST/ALT units/L N/A N/A Any Dose (% of original dose) No dose adjustment is recommended. No formal studies conducted. Initiate treatment at 0.7mg/m2. The dose may be escalated to 1mg/m2 or reduced to 0.5mg/m2 in subsequent cycles based on patient tolerability. Renal Impairment Drug Creatinine Clearance (ml/min) Isatuximab N/A 30 to 50 Lenalidomide Less than 30 Less than 30 with Dialysis Bortezomib N/A Dose (% of original dose) No dose adjustment is recommended. 10mg once daily. The dose may be escalated to 15 mg once daily after 2 cycles if patient is not responding to treatment and is tolerating the treatment. 7.5mg once daily or 15mg every other day. 5mg once daily. For dialysis patients, lenalidomide should be given after the procedure. No dose adjustment is recommended. For dialysis patients, bortezomib should be given after the procedure. Peripheral Neuropathy Bortezomib Severity Recommendation G1, no pain or loss of function None G1 with pain or G2 G2 with pain or G3 G4 and/or severe autonomic neuropathy Reduce to 1.0 mg/m2 Withhold treatment until symptoms of toxicity have resolved. When toxicity resolves re-initiate treatment at 0.7 mg/m2. Discontinue Version 1 (October 2025) Page 5 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide Other Lenalidomide Dose adjustments, during treatment and restart of treatment, are recommended to manage Grade 3 or 4 toxicities judged to be related to lenalidomide. Cardiac Failure Cardiac failure is a known common adverse reaction associated with lenalidomide treatment (ie occurs in between 1/10 and 1/100 patients who take lenalidomide). In most cases, this side effect occurs in patients with cardiac disease or cardiac risk factors and within six months of starting lenalidomide. Lenalidomide can cause atrial fibrillation, which may precipitate cardiac failure. Monitor for signs and symptoms of cardiac impairment. Cataract Cataract has been reported with a higher frequency in patients receiving lenalidomide in combination with dexamethasone particularly when used for a prolonged time. Regular monitoring of visual ability is recommended. Interstitial Lung Disease Interstitial lung disease (ILD), including cases of pneumonitis, have been observed with lenalidomide. Careful assessment of patients with an acute onset or unexplained worsening of pulmonary symptoms should be performed to exclude ILD. Lenalidomide should be interrupted during investigation of these symptoms and if ILD is confirmed, appropriate treatment should be initiated. Lenalidomide should only be resumed after a thorough evaluation of the benefits and the risks. Myocardial infarction Myocardial infarction has been reported in patients receiving lenalidomide in combination with dexamethasone particularly in those with known risk factors and within the first 12 months. Close monitoring is recommended. Pregnancy Lenalidomide is highly teratogenic. All prescribers, patients and pharmacy staff must comply with the manufacturer’s Pregnancy Prevention Programme. Women of child-bearing potential taking thalidomide must use one agreed effective method of contraception for at least 4 weeks before starting thalidomide, while on Lenalidomide and for one month after. They must have a negative pregnancy test within 3 days prior to starting treatment. Pregnancy testing should be repeated monthly thereafter until one month after stopping Lenalidomide (or every 2 weeks in women with irregular menstrual cycles). If a woman taking Lenalidomide thinks she may be pregnant she must stop the drug immediately and seek medical advice. Men taking Lenalidomide must use a barrier method of contraception throughout treatment and for one week after stopping, if their partner is capable of bearing children. Progressive Multifocal Leukoencephalopathy Progressive multifocal leukoencephalopathy (PML) has been reported with lenalidomide. Patients should be monitored for new or worsening neurological symptoms, cognitive or behavioural signs and symptoms. If PML is suspected, further dosing must be suspended Version 1 (October 2025) Page 6 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide until PML has been excluded. If PML is confirmed, lenalidomide must be permanently discontinued Reactivation of Hepatitis B Virus Hepatitis B virus reactivation has been reported in patients treated with lenalidomide. All patients must be screened for hepatitis B before initiation of treatment. This includes all patients with unknown serology who are on treatment already. Monitoring is required for patients with positive serology for clinical and laboratory signs of hepatitis B reactivation during treatment and for at least six months after completion of lenalidomide. Those with positive serology must seek medical help immediately if they experience symptoms of hepatitis B. Lenalidomide must be stopped if hepatitis B reactivation occurs during treatment. Skin Rash Lenalidomide must be discontinued for angioedema, anaphylactic reactions, exfoliative or bullous rash, or if Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN) or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is suspected, and should not be resumed following discontinuation from these reactions. Venous Thromboembolism (VTE) The combination of lenalidomide with dexamethasone is associated with an increased risk of venous thromboembolism. Appropriate thromboprophylaxis is recommended, especially in patients with additional thrombotic risk factors. If the patient develops thromboembolic events, treatment must be discontinued. Once the patient has been stabilised on the anticoagulation treatment and any complications of the thromboembolic event have been managed, the lenalidomide treatment may be restarted at the original dose dependent upon a benefit risk assessment. Regimen Cycle 1 (Initiation) Drug Isatuximab Dose 10mg/kg Days 1,8,15 and 22 Lenalidomide 15mg at bedtime 1-21 (inclusive) Administration Intravenous infusion in 250ml sodium chloride 0.9% at a variable rate Oral Bortezomib Dexamethasone 1.3mg/m2 20mg 1,8,15 and 22 1,2,8,9,15,16,22 and 23 SC Oral Reduce dose to 10mg (or iv dose equivalent) in over 75 yrs Cycle 2 to 8 (Initiation) Drug Dose Isatuximab 10mg/kg Days 1 and 15 Lenalidomide 15mg at bedtime 1-21 (inclusive) Administration Intravenous infusion in 250ml sodium chloride 0.9%at a variable rate Oral Version 1 (October 2025) Page 7 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide Bortezomib Dexamethasone 1.3mg/m2 20mg 1,8,15 and 22 1,2,8,9,15,16,22 and 23 SC Oral Reduce dose to 10mg (or iv dose equivalent) in over 75yrs Cycle 9 to 19 (Maintenance) Drug Dose Isatuximab 10mg/kg Days 1 and 15 Lenalidomide 15mg at bedtime 1-21 (inclusive) Dexamethasone 20mg 1 and 15 Administration Intravenous infusion in 250ml sodium chloride 0.9%at a variable rate Oral Oral Reduce dose to 10mg (or iv dose equivalent) in over 75yrs Cycle 20 onwards (Maintenance) Drug Dose Isatuximab 10mg/kg Days 1 Lenalidomide 15mg at bedtime 1-21 (inclusive) Dexamethasone 20mg 1 Administration Intravenous infusion in 250ml sodium chloride 0.9%at a variable rate Oral Oral Reduce dose to 10mg (or iv dose equivalent) in over 75yrs Cycle Frequency 28-day cycle until disease progression or unacceptable toxicity (Initiation and Maintenance cycles to be set separately on Aria) (12 cycles of cycle 20 to be set) Dose Information • The dose of dexamethasone should be reduced to 10mg in those over 75 years of age. • Dexamethasone is available as 500microgram, 2mg and 4mg tablets and as a 2mg/5ml oral liquid. • Isatuximab and Bortezomib to be dose banded in accordance with national dose banding • Lenalidomide is available as 2.5mg, 5mg, 7.5mg, 10mg, 15mg, 20mg, and 25mg capsules. Version 1 (October 2025) Page 8 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide Administration Information • For first dose a cannula should be inserted to allow emergency treatment of Anaphylaxis • Dexamethasone should be taken in the morning with or immediately after food. • Lenalidomide should be taken at the same time each day. The capsules should be swallowed whole, preferably with water, with or without food and not be opened, broken or chewed. • Lenalidomide can cause drowsiness it may be advisable to take it at night. • If a dose of lenalidomide is forgotten on one day, the normal prescribed dose should be taken the next day. Patients should not adjust the dose to make up for missing a dose on previous days. • All prescriptions for lenalidomide must be accompanied by a prescription authorisation form (PAF). • The rate of isatuximab administration varies and depends on infusion related reactions. In order to determine the rate of the second and ongoing infusions all reactions and the first reaction free infusion must be recorded in the ARIA journal. • Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an in-line, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC or PE administration sets must be used. First infusion Second infusion Subsequent infusionsa Final volume 250ml 250mL 250ml Initial rate (first hour) 25mL/hour 50mL/hour 200mL/hour Rate incrementa If absence of infusion reaction for 60 minutes increase by 25mL/hour every 30 minutes 50mL and hour for 30 minutes then increase by 100mL/hour Maximum rate 150mL/hour 200mL/hour 200mL/hour a Consider the incremental escalation of the infusion rate only in the absence of infusion reactions with the previous infusion Administration adjustments should be made if patients experience infusion reactions. In patients who experience Grade 2 (moderate) infusion reactions, a temporary interruption in the infusion should be considered and additional symptomatic medicinal products can be Version 1 (October 2025) Page 9 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide administered. After improvement to grade ≤1 (mild), isatuximab infusion may be resumed at half of the initial infusion rate under close monitoring and supportive care, as needed. If symptoms do not recur after 30 minutes, the infusion rate may be increased to the initial rate, and then increased incrementally, as shown in the table above. If symptoms do not resolve rapidly or do not improve to Grade ≤1 after interruption of isatuximab infusion, recur after initial improvement with appropriate medicinal products, or require hospitalization or are life-threatening (Grade ≥3), treatment with isatuximab should be permanently discontinued and additional supportive therapy should be administered, as needed. Check vital signs before the start of the infusion, every 15 minutes during the first 60 minutes of the infusion and at the end of the infusion for all isatuximab infusions. Additional therapy • Thromboprophylaxis, the choice depending on risk factors and duration of therapy. Low molecular weight heparin or DOAC is preferred above aspirin unless there are other clinical reasons to guide thromboprophylaxis. • Allopurinol 300mg once a day for seven days for the first cycle only oral • Premedication required 15 – 60 minutes before satuximab infusion on cycles 1 and 2: - Dexamethasone – see regimen for dose details - Chlorphenamine 10mg intravenous - Omeprazole 20mg oral - Paracetamol 1000mg oral Pre-meds for further cycles are set in ARIA but can be removed as per clinician discretion • Consider anti-infective prophylaxis including; - Aciclovir 400mg twice a day oral - Co-trimoxazole 960mg once a day oral on Monday, Wednesday and Friday only • Bisphosphonates and calcium/vitamin D in accordance with local policies. • Mouthwashes according to local or national policy on the treatment of mucositis. • Gastric protection with a proton pump inhibitor or a H2 antagonist may be considered in patients considered at high risk of GI ulceration or bleed. • As required for the treatment of infusion related reactions for patients at high risk of respiratory complications; - sodium chloride 0.9% 500ml intravenous - salbutamol 2.5mg nebulised - hydrocortisone sodium succinate 100mg intravenous - chlorphenamine 10mg intravenous - paracetamol 1000mg oral - oxygen as required Version 1 (October 2025) Page 10 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide Additional Information • The National Patient Safety Alert on oral chemotherapy (NPSA/2008/RRR001) must be followed in relation to lenalidomide. • For all patients taking lenalidomide; the patient, prescriber and supplying pharmacy must comply with the Celgene pregnancy prevention programme (PPP). • All instances of infusion related reaction must be recorded on ARIA. Isatuximab will continue to be administered at the cycle one rate until a reaction free infusion is noted. • Isatuximab interferes with indirect antiglobulin tests as it binds to CD38 on red blood corpuscles (RBCs) and interferes with compatibility testing, including antibody screening and cross matching. Isatuximab interference mitigation methods include treating reagent RBCs with dithiothreitol (DTT) to disrupt isatuximab binding or other locally validated methods. Since the Kell blood group system is also sensitive to DTT treatment, Kell-negative units should be supplied after ruling out or identifying alloantibodies using DTT-treated RBCs. Alternatively, phenotyping or genotyping may also be considered. • Isatuximab may be detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for monitoring disease monoclonal immunoglobulins (M protein). This can lead to false positive SPE and IFE assay results for patients with IgG kappa myeloma protein impacting initial assessment of complete responses by International Myeloma Working Group (IMWG) criteria. In patients with persistent very good partial response, consider other methods to evaluate the depth of response. References 1. Lenalidomide Mylan 10mg Hard Capsules (2025). Summary of Product Characteristics. Electronic Medicines Compendium. Online at https://www.nice.org.uk/guidance/ta1098, accessed 1 October 2025. 2. National Institute for Health and Care Excellence (2025). Isatuximab in combination for untreated multiple myeloma when a stem cell transplant is unsuitable [TA1098]. London: National Institute for Health and Care Excellence. 3. Celgene Limited (2025). Revlimid (Lenallidomide) Healthcare Professionals Information Pack UK Version 11. 4. Facon T, Dimopoulos MA, Xavier P et al. Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. The New England Journal of Medicine (2024); 391: 1597-1609. Version 1 (October 2025) Page 11 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide REGIMEN SUMMARY Isa-VRD weekly Isatuximab-Lenalidomide-Bortezomib-Dexamethasone (20) Cycle 1 Day 1 Warning – Check blood transfusion status Administration Instructions Patients treated with isatuximab carry a lifelong risk of transfusion associated graft versus host disease. Where blood products are required these patients must receive ONLY IRRADIATED BLOOD PRODUCTS for life. Ensure transfusion departments are notified and the patient has been issued with an alert card to carry at all times. 1. Chlorphenamine 10mg intravenous Administration Instructions Administer 15 – 60 minutes prior to Isatuximab 2. Warning – Dexamethasone Dose in Elderly Administration Instructions In those aged over 75 years reduce the dose of dexamethasone to 10mg once a day orally or equivalent intravenous dose 3. Dexamethasone 20mg oral Administration Instructions Administer 15 – 60 minutes prior to Isatuximab Administer 20mg once a day orally. For those unable to tolerate the oral route this can be administered at an equivalent intravenous dose. Reduce dose to 10mg orally or intravenous equivalent if the patient is over 75 years old. 4. Paracetamol 1000mg oral Administration Instructions Administer 15 – 60 minutes prior to Isatuximab Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 5. Omeprazole 20mg Oral Administration Instructions Administer 15 – 60 minutes prior to Isatuximab 6. Isatuximab 10mg/kg in 250ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of isatuximab administration varies and is dependant the occurrence and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC or PE administration sets must be used. 7. Bortezomib 1.3mg/m2 subcutaneous injection 8. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 9. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 10. Paracetamol 1000mg oral when required for the relief of infusion related reactions Administration Instructions Please check if the patient takes regular paracetamol for pain control and take dose into account 11. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions 12. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Version 1 (October 2025) Page 12 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide Cycle 1 Day 8, 15 and 22 Warning – Check blood transfusion status Administration Instructions Patients treated with isatuximab carry a lifelong risk of transfusion associated graft versus host disease. Where blood products are required these patients must receive ONLY IRRADIATED BLOOD PRODUCTS for life. Ensure transfusion departments are notified and the patient has been issued with an alert card to carry at all times. 13. Chlorphenamine 10mg intravenous Administration Instructions Administer 15 – 60 minutes prior to Isatuximab 14. Warning – Check if the Dexamethasone Taken Administration Instructions Ensure the patient has taken the dexamethasone premedication. If not please administer dexamethasone 20mg oral or intravenous if the patient is unable to tolerate the oral dose. Reduce dose to 10mg intravenous equivalent or 10mg orally in patients over 75 years old. 15. Warning – Check if the Paracetamol Taken Administration Instructions Please check if the patient has taken paracetamol. If not please administer paracetamol 1000mg. The maximum dose is 4000mg/24 hours 16. Omeprazole 20mg Oral Administration Instructions Administer 15 – 60 minutes prior to Isatuximab 17. Isatuximab 10mg/kg in 250ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of isatuximab administration varies and is dependant the occurrence and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC or PE administration sets must be used. 18. Bortezomib 1.3mg/m2 subcutaneous injection 19. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 20. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 21. Paracetamol 1000mg oral when required for the relief of infusion related reactions Administration Instructions Please check if the patient takes regular paracetamol for pain control and take dose into account 22. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions 23. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Take home medicines (day 1 only) 24. Warning – Pregnancy Prevention Programme Administration Instructions Lenalidomide is associated with a pregnancy prevention programme. Please ensure this is completed for all patients. 25. Lenalidomide 15mg once a day on days 1-21 oral Administration Information Oral SACT Version 1 (October 2025) Page 13 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide Pregnancy prevention programme Take at the same time each day. Swallow the capsules whole, preferably with water, with or without food. 26. Dexamethasone 20mg Oral on days 2, 8, 9, 15,16, 22 and 23. Administration Instructions Reduce dose to 10mg orally or intravenous equivalent if the patient is over 75 years old. Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice. 27. Dexamethasone 20mg Oral on days 1 of the next cycle Take in the morning prior to Isatuximab injection. Note to pharmacy; dispense for day 1 of the next cycle 28. Allopurinol 300mg once a day for 7 days, oral Administration information Take in the morning with food and plenty of water. This should be supplied for the first cycle only. 29. Aciclovir 400mg twice a day for 28 days oral Administration Instructions Please supply 28 days or an original pack if appropriate. 30. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 28 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 28 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice. 31. Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - esomeprazole 20mg once a day oral - omeprazole 20mg once a day oral - lansoprazole 15mg once a day oral - pantoprazole 20mg once a day oral - rabeprazole 20mg once a day oral - cimetidine 400mg twice a day oral - famotidine 20mg once a day oral - nizatidine 150mg twice a day oral Please supply 28 days or the nearest original pack size. 32. Thromboprophylaxis according to risk factors Administration Instructions The choice of thromboprophylaxis is dependent on local formularly choice and may include; - dalteparin 5000units once a day subcutaneous injection - enoxaparin 40mg once a day subcutaneous injection - heparin 5000units twice a day subcutaneous injection - apixaban 2.5mg TWICE a day ORAL or equivalent NOAC Please supply 28 days or nearest original pack size. Aspirin may be considered after cycle six of treatment. 33. Paracetamol 1000mg oral on the days of daratumumab administration Administration Instructions Take 1000mg prior to Isatuximab administration. To be taken 1 - 3 hours prior to isatuximab infusion Please supply 1 x 100 x 500mg. This is to cover all cycles Cycle 2 to 8 Days 1 and 15 34. Chlorphenamine 10mg intravenous Administration Instructions Administer 15 – 60 minutes prior to Isatuximab 35. Warning – Check if the Dexamethasone Taken Administration Instructions Ensure the patient has taken the dexamethasone premedication. If not please administer dexamethasone 20mg oral or intravenous if the patient is unable to tolerate the oral dose. Reduce dose to 10mg intravenous equivalent or 10mg Version 1 (October 2025) Page 14 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide orally in patients over 75 years old. 36. Warning – Check if the Paracetamol Taken Administration Instructions Please check if the patient has taken paracetamol. If not please administer paracetamol 1000mg. The maximum dose is 4000mg/24 hours 37. Omeprazole 20mg Oral Administration Instructions Administer 15 – 60 minutes prior to Isatuximab 38. Isatuximab 10mg/kg in 250ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of isatuximab administration varies and is dependant the occurrence and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC or PE administration sets must be used. 39. Bortezomib 1.3mg/m2 subcutaneous injection 40. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 41. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 42. Paracetamol 1000mg oral when required for the relief of infusion related reactions Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 43. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions 44. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Take home medicines (day 1 only) 45. Warning – Pregnancy Prevention Programme Administration Instructions Lenalidomide is associated with a pregnancy prevention programme. Please ensure this is completed for all patients. 46. Dexamethasone 20mg Oral on days 2, 8, 9, 15,16,22 and 23 Administration Instructions Reduce dose to 10mg orally or intravenous equivalent if the patient is over 75 years old. Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice. 47. Dexamethasone 20mg Oral on days 1 of the next cycle Administration Instructions Administer 15 – 60 minutes prior to Isatuximab Administer 20mg once a day orally. For those unable to tolerate the oral route this can be administered at an equivalent intravenous dose. Reduce dose to 10mg orally or intravenous equivalent if the patient is over 75 years old. 48. Lenalidomide 15mg once a day on days 1-21 oral Administration Information Oral SACT Pregnancy prevention programme Take at the same time each day. Swallow the capsules whole, preferably with water, with or without food. 49. Aciclovir 400mg twice a day for 28 days oral Version 1 (October 2025) Page 15 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide Administration Instructions Please supply 28 days or an original pack if appropriate. 50. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 28 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 28 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice. 51. Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - esomeprazole 20mg once a day oral - omeprazole 20mg once a day oral - lansoprazole 15mg once a day oral - pantoprazole 20mg once a day oral - rabeprazole 20mg once a day oral - cimetidine 400mg twice a day oral - famotidine 20mg once a day oral - nizatidine 150mg twice a day oral - ranitidine 150mg twice a day oral Please supply 28 days or the nearest original pack size. 52. Thromboprophylaxis according to risk factors Administration Instructions The choice of thromboprophylaxis is dependent on local formularly choice and may include; - dalteparin 5000units once a day subcutaneous injection - enoxaparin 40mg once a day subcutaneous injection - heparin 5000units twice a day subcutaneous injection - apixaban 2.5mg TWICE a day ORAL or equivalent NOAC Please supply 28 days or nearest original pack size. Aspirin may be considered after cycle six of treatment. Cycle 2 to 8 Days 8 and 22 53. Bortezomib 1.3mg/m2 subcutaneous injection Cycle 9 to 19 Days 1 and 15 54. Chlorphenamine 10mg intravenous Administration Instructions Administer 15 – 60 minutes prior to Isatuximab 55. Warning – Check if the Dexamethasone Taken Administration Instructions Ensure the patient has taken the dexamethasone premedication. If not please administer dexamethasone 20mg oral or intravenous if the patient is unable to tolerate the oral dose. Reduce dose to 10mg intravenous equivalent or 10mg orally in patients over 75 years old. 56. Warning – Check if the Paracetamol Taken Administration Instructions Please check if the patient has taken paracetamol. If not please administer paracetamol 1000mg. The maximum dose is 4000mg/24 hours 57. Omeprazole 20mg Oral Administration Instructions Administer 15 – 60 minutes prior to Isatuximab 58. Isatuximab 10mg/kg in 250ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of isatuximab administration varies and is dependant the occurrence and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Version 1 (October 2025) Page 16 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide Polyurethane (PU), polybutadiene (PBD), PVC or PE administration sets must be used. 59. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 60. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 61. Paracetamol 1000mg oral when required for the relief of infusion related reactions Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 62. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions 63. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Take home medicines (day 1 only) 64. Warning – Pregnancy Prevention Programme Administration Instructions Lenalidomide is associated with a pregnancy prevention programme. Please ensure this is completed for all patients. 65. Dexamethasone 20mg Oral on day 15 Administration Instructions Reduce dose to 10mg orally or intravenous equivalent if the patient is over 75 years old. Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice. 66. Dexamethasone 20mg Oral on days 1 of the next cycle Take in the morning prior to Isatuximab injection. Note to pharmacy; dispense for day 1 of the next cycle 67. Lenalidomide 15mg once a day on days 1-21 oral Administration Information Oral SACT Pregnancy prevention programme Take at the same time each day. Swallow the capsules whole, preferably with water, with or without food. 68. Aciclovir 400mg twice a day for 28 days oral Administration Instructions Please supply 28 days or an original pack if appropriate. 69. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 28 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 28 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice. 70. Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - esomeprazole 20mg once a day oral - omeprazole 20mg once a day oral - lansoprazole 15mg once a day oral - pantoprazole 20mg once a day oral - rabeprazole 20mg once a day oral - cimetidine 400mg twice a day oral - famotidine 20mg once a day oral - nizatidine 150mg twice a day oral - ranitidine 150mg twice a day oral Version 1 (October 2025) Page 17 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide Please supply 28 days or the nearest original pack size. 71. Thromboprophylaxis according to risk factors Administration Instructions The choice of thromboprophylaxis is dependent on local formularly choice and may include; - dalteparin 5000units once a day subcutaneous injection - enoxaparin 40mg once a day subcutaneous injection - heparin 5000units twice a day subcutaneous injection - apixaban 2.5mg TWICE a day ORAL or equivalent NOAC Please supply 28 days or nearest original pack size. Aspirin may be considered after cycle six of treatment. Cycle 20 onwards Day 1 72. Chlorphenamine 10mg intravenous Administration Instructions Administer 15 – 60 minutes prior to Isatuximab 73. Warning – Check if the Dexamethasone Taken Administration Instructions Ensure the patient has taken the dexamethasone premedication. If not please administer dexamethasone 20mg oral or intravenous if the patient is unable to tolerate the oral dose. Reduce dose to 10mg intravenous equivalent or 10mg orally in patients over 75 years old. 74. Warning – Check if the Paracetamol Taken Administration Instructions Please check if the patient has taken paracetamol. If not please administer paracetamol 1000mg. The maximum dose is 4000mg/24 hours 75. Omeprazole 20mg Oral Administration Instructions Administer 15 – 60 minutes prior to Isatuximab 76. Isatuximab 10mg/kg in 250ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of isatuximab administration varies and is dependant the occurrence and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC or PE administration sets must be used. 77. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 78. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 79. Paracetamol 1000mg oral when required for the relief of infusion related reactions Administration Instructions Please check if the patient takes regular paracetamol for pain control and take dose into account 80. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions 81. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Take home medicines (day 1 only) 82. Dexamethasone 20mg Oral on days 1 of the next cycle Take in the morning prior to Isatuximab injection. Note to pharmacy; dispense for day 1 of the next cycle. Version 1 (October 2025) Page 18 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide 83. Warning – Pregnancy Prevention Programme Administration Instructions Lenalidomide is associated with a pregnancy prevention programme. Please ensure this is completed for all patients. 84. Lenalidomide 15mg once a day on days 1-21 oral Administration Information Oral SACT Pregnancy prevention programme Take at the same time each day. Swallow the capsules whole, preferably with water, with or without food. 85. Aciclovir 400mg twice a day for 28 days oral Administration Instructions Please supply 28 days or an original pack if appropriate. 86. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 28 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 28 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice. 87. Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - esomeprazole 20mg once a day oral - omeprazole 20mg once a day oral - lansoprazole 15mg once a day oral - pantoprazole 20mg once a day oral - rabeprazole 20mg once a day oral - cimetidine 400mg twice a day oral - famotidine 20mg once a day oral - nizatidine 150mg twice a day oral - ranitidine 150mg twice a day oral Please supply 28 days or the nearest original pack size. 88. Thromboprophylaxis according to risk factors Administration Instructions The choice of thromboprophylaxis is dependent on local formularly choice and may include; - dalteparin 5000units once a day subcutaneous injection - enoxaparin 40mg once a day subcutaneous injection - heparin 5000units twice a day subcutaneous injection - apixaban 2.5mg TWICE a day ORAL or equivalent NOAC Please supply 28 days or nearest original pack size. Aspirin may be considered after cycle six of treatment. . Version 1 (October 2025) Page 19 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide DOCUMENT CONTROL Version Date Amendment Written By Approved By 1 October 2025 None Noriko Kendall Pharmacist Noel Ryman Consultant Haematologist This chemotherapy protocol has been developed as part of the chemotherapy electronic prescribing project. This was and remains a collaborative project that originated from the former CSCCN. These documents have been approved on behalf of the following Trusts; Hampshire Hospitals NHS Foundation Trust NHS Isle of Wight Portsmouth Hospitals NHS Trust Salisbury NHS Foundation Trust University Hospital Southampton NHS Foundation Trust Western Sussex Hospitals NHS Foundation Trust All actions have been taken to ensure these protocols are correct. However, no responsibility can be taken for errors that occur as a result of following these guidelines. Version 1 (October 2025) Page 20 of 20 Myeloma – Isatuximab-Bortezomib-Dexamethasone (20)-Lenalidomide
Url
/Media/UHS-website-2019/Docs/Chemotherapy-SOPs1/Myeloma/Isatuximab-VRD-weekly-Ver1.pdf
Two duties of candour
Description
In the summer of 2015, the views of the Department of Health (DH), the Nursing and Midwifery Council (NMC) and the General Medical Council (GMC) on the implementation of the duty of candour finally became clear.
Url
/HealthProfessionals/Clinical-law-updates/Twodutiesofcandour.aspx
Papers Council of Governors 20 July 2022
Description
Agenda attachments 1 CoG Agenda - 20.07.2022.docx Date Time Location Chair Agenda Council of Governors 20/07/2022 14:00 - 15:30 Microsoft Teams Jenni Douglas-Todd 1 Chair’s Welcome and Opening Comments 14:00 2 Declarations of Interest 14:02 3 Minutes of Previous Meeting 14:03 Approve the minutes of the previous meeting held on 27 April 2022 4 Matters Arising/Summary of Agreed Actions 14:04 5 Strategy, Quality and Performance 5.1 Chief Executive Officer's Performance Report 14:06 Receive and note the report Sponsor: David French, Chief Executive Officer Attendee: Gail Byrne, Chief Nursing Officer 5.2 Strategic Objectives (Oral) 14:26 Review and feedback on the Strategic Objectives Sponsor: David French, Chief Executive Officer Attendee: Christine McGrath, Director of Strategy and Partnerships 6 Governance 6.1 Non-Executive Director Reappointment and Appointment of Deputy Chair 14:41 • Approve Tim Peachey’s reappointment as a non-executive director for a second three year term commencing on 1 October 2022 on the same terms and conditions as his current appointment • Approve the recommendation to defer the appointment of a deputy chair to the meeting on 19 October 2022 following a recommendation made by the newly appointed chair Sponsor: Jenni Douglas-Todd, Trust Chair Attendee: Helen Potton, Interim Associate Director of Corporate Affairs and Company Secretary 6.2 Amendments to the Constitution 14:51 Approve the proposed amendments to the Trust’s constitution Sponsor: Jenni Douglas-Todd, Trust Chair Attendee: Helen Potton, Interim Associate Director of Corporate Affairs and Company Secretary 6.3 Appointment of Lead Governor 14:56 Note the proposal to appoint the Lead Governor Sponsor: Jenni Douglas-Todd, Trust Chair Attendee: Helen Potton, Interim Associate Director of Corporate Affairs and Company Secretary 7 Membership Engagement and Governor Activity 7.1 Membership Engagement 15:01 Receive the report Sponsor: David French, Chief Executive Officer Attendee: Karen Burwell, Communications and Marketing Manager 7.2 Feedback from Governors' Nomination Committee 15:06 Chair: Jenni Douglas-Todd, Trust Chair 7.3 Feedback from Strategy and Finance Working Group 15:09 Chair: Tim Waldron 7.4 Feedback from Patient and Staff Experience Working Group 15:12 Chair: Forkanul Quader 7.5 Feedback from Membership and Engagement Working Group 15:15 Chair: Bob Purkiss 8 Review of Meeting 15:18 Review and feedback on the content of this meeting Sponsor: Jenni Douglas-Todd, Trust Chair 9 Any other business 15:23 Raise any relevant or urgent matters that are not on the agenda 10 Date of next meeting: 19 October 2022 15:28 Note the date of the next meeting 11 Resolution regarding the press, public and others 15:29 Agree, as permitted by the National Health Service Act 2006 (as amended), the Trust's Constitution and the Standing Orders of the Council of Governors, that representatives of the press, members of the public and others not invited to attend to the next part of the meeting be excluded due to the confidential nature of the business to be transacted Sponsor: Jenni Douglas-Todd, Trust Chair Page 2 3 Minutes of Previous Meeting 1 3 COG Minutes Draft - 27.04.2022 final.pdf Minutes - Council of Governors (CoG) Date Time Location Chair Present In attendance Apologies 27 April 2022 14.00-16.00 Microsoft Teams Jane Bailey, Interim Chair Jane Bailey, Interim Chair Dr Diane Bray, Appointed, Solent University Dr Nigel Dickson, Elected, New Forest, Eastleigh and Test Valley Helen Eggleton, Appointed, NHS Hampshire, Southampton and Isle of Wight CCG Harry Hellier, Elected, New Forest, Eastleigh and Test Valley Kelly Lloyd, Elected, Health Professional and Health Scientist Staff Councillor Alexis McEvoy, Appointed, Hampshire County Council Robert Purkiss, Elected, Rest of England and Wales (until item 6.4) Forkanul Quader, Elected, Southampton City Catherine Rushworth, Elected, Isle of Wight Councillor Rob Stead, Appointed, Southampton City Council (until item 6.5) Werner Struss, Elected, Medical Practitioners and Dental Staff Amanda Turner, Elected, Non-Clinical and Support Staff Quintin van Wyk, Elected, Rest of England and Wales Sam Dolton, Events and Membership Officer Karen Flaherty, Associate Director of Corporate Affairs Ian Howard, Chief Financial Officer (for items 5.1 and 5.2) David French, Chief Executive Officer (for item 5.3) Tim Peachey, Non-Executive Director (NED) Karen Russell, Council of Governors’ Business Manager Asa Thorpe, Associate Director – Commercial (for item 5.2) Theresa Airiemiokhale, Elected, Southampton City Katherine Barbour, Elected, Southampton City Professor Mandy Fader, Appointed, University of Southampton Tim Waldron, Elected, Southampton City JB DB ND HE HH KL AM RP FQ CR RS WS AT QvW SD KF IH DAF TP KR ATh TA KBa MF TW 1 Chair’s Welcome and Opening Comments The Chair welcomed everyone to the meeting and, in particular, WS who was attending a meeting of the CoG for the first time since becoming a governor. 2 Declarations of Interest There were no new declarations of interest relating to matters on the agenda. 3 Minutes of Previous Meeting The minutes of the meeting held on 26 January 2022 were approved as an accurate record of the meeting. 4 Matters Arising/Summary of Agreed Actions The updates on the actions in the paper were noted. The review of the CoG’s 1 composition had been considered by the CoG Membership and Engagement Working Group at its most recent meeting and a progress update would be provided later in the meeting. 5 Strategy, Quality and Performance 5.1 Operational Plan 2022/23 IH, who was attending the meeting to present this item, advised that the operational plan for 2022/23 had also been presented to the CoG Strategy and Finance Working Group at its meeting on 21 April 2022. The purpose of the paper was to inform the CoG about aspects of the Trust’s operating environment and plan for 2022/23. The following areas were summarised: • the Trust’s income for 2022/23 was broadly level with 2021/22 and the expectation was that 104% of the 2019/20 levels of elective activity would be delivered with this level of funding, through increased efficiency improvement valued at £33 million; • there were planned operating deficits across the NHS and the Trust’s deficit of £19.5 million was attributable to factors outside of its control, including costs associated with COVID-19, increased energy prices and general inflationary pressures; and • there were plans for continued recruitment and retention to increase employed staff by a further 478 full-time equivalent staff, to be funded through planned reductions in the use of bank and agency staff hours. In response to questions raised IH confirmed: • the Trust’s specialities with the patients waiting longest (over 18 months and two years) were: o trauma and orthopaedics, where procedures were of lower clinical priority and had been deferred for that reason; and o ear, nose and throat, where activity had reduced because of infection prevention and control measures related to aerosol generating procedures; and • although recruitment to fill vacancies was continuing there was no funding for new posts, however, additional investment in staffing would be required in 2023/24 and 2024/25 to meet the expected increase in elective activity to reduce waiting lists further. 5.2 Non-NHS Activity This item had also been discussed by the CoG Strategy and Finance Working Group at its meeting on 21 April 2022. The Trust’s private patient income for 2021/22 was forecast to be approximately £6.4 million, which represented just under 0.7% of the Trust’s overall income. The growth in activity had been due to more complex patients being treated, whilst maintaining the prioritisation of clinically urgent procedures in the context of the unprecedented pressure on core NHS services. Private patient activity was expected to remain at similar levels for at least the next six months. The income from non-NHS activity, including private patient activity, was reinvested into NHS services and to support further innovation and activity. Non-NHS income was also derived from the following: • the commercialisation of Trust-derived intellectual property with an expected forecast of at least £140,000 in 2022/23; • the co-development of innovative medical technology, for which the income forecast was £150,000 for 2022/23; and • advertising income from the electronic screens located in patient areas 2 around the hospitals. Details of a range of the innovative therapies, treatments and projects being developed by the Trust were shared with governors. Decisions: • The CoG confirmed that it was satisfied that the Trust’s non-NHS activity would not significantly interfere with its principal purpose, which was to provide goods and services for the health service in England, or the performance of its other functions. • The CoG authorised the Trust Chair to inform the board of directors (Board) of its decision. 5.3 Chief Executive Officer’s Performance Report DAF joined the meeting to present the performance report and provided an update since the period of December 2021 to February 2022 covered by the report. He highlighted that: • March and April 2022 had been very challenging for the NHS nationally due to the high levels of COVID-19 among patients in hospital for other reasons, and in norovirus reflecting the prevalence of these viruses in the community; • the Trust’s staff absence rates had increased to 6% at times from approximately 3% normally due to staff having COVID-19 or self-isolating; • there were consistently 180 patients in the hospitals who were medically optimised for discharge (MOFD), however, continuing levels of staff absence in community and domiciliary care services and in care homes were leading to delays in discharge for patients needing further support following discharge or with longer-term care needs; • attendances in the emergency department were increasingly high and the Trust’s emergency access performance had been impacted negatively by the number of attendances, including the Trust’s approach to ambulance handovers, which resulted in fewer ambulances queuing but more patients in the department; • the volume of non-elective urgent activity and the number of patients MOFD had regrettably led to the cancellation of elective activity, which had both a practical and emotional impact on those patients whose surgery was delayed; • cases of COVID-19 and norovirus in the Trust had dropped substantially in the previous two weeks and the focus had moved to delivering the Trust’s programme of elective activity; • the number of patients waiting over 104 weeks had reduced to five by the end of March 2022 and the Trust was confident that this would be zero by July 2022; • the Trust had increased both physical and workforce capacity through investment over the previous few years, however there was still insufficient capacity, and this was being addressed through the creation of clinical networks with partners and improvement programmes in theatres, outpatients and patient flow through the hospitals; and • recruitment and retention of staff was more difficult in an increasingly competitive employment market, however, in the NHS staff survey 2021, the Trust had scored highly among staff recommending it to care for family and friends (fifth in its peer group) and recommending it as a place to work (seventh in its peer group). In response to a question from CR, DAF confirmed that the Trust did offer incentive payments to staff who worked additional shifts, however, substantive recruitment 3 was the solution to ensure a good work life balance and overall wellbeing for staff. In response to a query from FQ regarding the expected performance of the Trust in six months’ time, DAF agreed it was difficult to predict however, he hoped that there would significantly fewer cases of COVID-19 and elective activity would return to levels achieve previously and the Trust could deliver comparative performance in the top quartile. The next few years would be very difficult for the NHS generally as it reduced waiting times and the number of patients waiting. While the Trust’s plans to reduce waiting lists were achievable, capacity would continue to be an issue for the Trust. The number of patients who were MOFD would have a bearing on this so the Trust would continue to work closely with health and social care partners to facilitate the timely discharge of patients. The plans to open a new elective hub at Winchester Hospital within the next 18 months would also provide additional capacity and clinical, managerial and finance teams at the trusts involved were committed to making this work. In response to a question from RP, DAF advised that the maternity friends and family test score had improved substantially in January and February 2022 as a result of an improvement plan put in place in the antenatal ward, and progress had been closely monitored by the Board. The response time for complaints had been increased from 35 to 55 days to recognise the demands upon clinical staff during the latest wave of the COVID-19 pandemic. There had also been a number of changes to personnel within the patient advice and liaison service (PALS) as staff had moved into other roles in the Trust. 5.4 Draft Quality Report and Annual Report Timetable NHS England and NHS Improvement (NHSE/I) had published the timetable for the 2021/22 annual report and accounts and associated guidance. While this had removed the requirements to produce a separate quality report, the quality accounts requirements set out in The National Health Service (Quality Accounts) Regulations 2010 still applied requiring trusts to produce quality accounts, including circulation of the quality accounts to commissioners, local authorities, local Healthwatch and the CoG for comment by the end of April 2022. The Trust had taken the decision to produce the annual report and accounts and the quality accounts on the same timetable as a single document by the submission deadline of 22 June 2022. However, due to the additional work required to complete the value for money external audit, the quality accounts were to be published as a separate document by 30 June 2022. The annual report and accounts would be published after they had been laid before Parliament, which was expected to occur at the beginning of September 2022. The timing of the meeting of the CoG at which the final annual report and accounts (including the quality accounts) and the external auditors’ report were to be presented would be later than usual to allow for these to be laid before Parliament as this would normally take place in July. An update would be provided to the CoG in a closed session of its meeting in July 2022 to mitigate the impact of this delay. The date of the annual members’ meeting would be finalised at a later date to ensure that the annual report and accounts were laid before Parliament before the annual members’ meeting took place. Governors had been invited to provide comments or feedback on the draft quality accounts for 2021/22 by 29 April 2022 and the formal response to the consultation from the CoG would be co-ordinated by RP as Lead Governor. 4 6 Governance 6.1 Non-Executive Director Reappointment The first three year term of office as a NED for Dave Bennett was to come to an end on 14 July 2022. NEDs were eligible for reappointment for a second three year term subject to reappointment by the CoG. When considering the reappointment of a NED, the CoG should consider: • the outcome of the NED’s appraisals since appointment; • their other commitments and the time available for the role; and • independence. The most recent appraisal of Dave Bennett was carried out in February 2022. Following appraisal, the then Chair, Peter Hollins, confirmed that Dave Bennett’s performance as a NED continued to be effective and demonstrated his commitment to the role and that he would have no hesitation in recommending Dave Bennett for reappointment to the role. Since his original appointment, Dave had ceased his commercial consultancy business, Davox Consulting Ltd, and had been appointed to the following NED/trustee roles: • Chairman, Royal College of General Practitioners (RCGP) Enterprises Ltd • Chairman, RCGP Conferences Ltd • NED, Faculty of Leadership and Medical Management (FMLM) • Director, FMLM Applied Ltd • Director/Trustee and Chair, YMCA Fairthorne Group. Dave had indicated his willingness to be reappointed for a further three year term and confirmed that he continued to have the time to commit to the role. The Governors’ Nomination Committee (GNC) had met on 26 April 2022 and had agreed to recommend that the CoG approve the reappointment without any need for process of open competition. Decision: The CoG approved Dave Bennett’s reappointment as a NED for a second three year term commencing on 15 July 2022 on the same terms and conditions as his current appointment. 6.2 Review Terms of Reference – Council of Governors and Working Groups The terms of reference for the Council of Governors and its working groups should be reviewed regularly, and at least once annually, to ensure that these reflected the purpose and activities of the CoG and each of the working groups. The terms of reference for the GNC were reviewed by the CoG at its meeting in October 2021 and so were not presented for review at this meeting. The terms of reference for the CoG’s working groups had been reviewed by the relevant working group prior to submission to the CoG. Minor changes were proposed to reflect changes to practice and strategies since the terms of reference were last reviewed. Decision: The CoG approved the revised terms of reference for the: • CoG; • CoG Membership and Engagement Working Group; • CoG Patient and Staff Experience Working Group; and • CoG Strategy and Finance Working Group 5 6.3 Council of Governors’ Election 2022 A number of vacancies within the CoG would arise on 1 October 2022 as current governors reached the end of their terms of office, following agreement of the CoG to fill existing vacancies at the scheduled election in 2022 and as a result of proposed changes to the composition of the CoG taking effect from 1 October 2022. Elections would take place in the following areas of the public constituency and classes of the staff constituency: • Isle of Wight - one vacancy; • Southampton City - five vacancies; • New Forest, Eastleigh and Test Valley - three vacancies for a term of three years and one vacancy with a remaining term of office of one year; • Rest of England and Wales - one vacancy with a remaining term of office of two years; • Non-clinical and support staff class - one vacancy; • Nursing and Midwifery staff class - one vacancy; As a result of the proposed changes to the composition of the CoG taking effect from 1 October 2022, a vacancy that would have arisen in the Rest of England and Wales public constituency would not be filled as the number of governors representing this constituency was to be reduced by one. The timetable for the elections had been prepared in accordance with the guidance specified in the model election rules. The elections would be conducted by an independent election service provider acting as the returning officer on behalf of the Trust. Four election service providers had been invited to provide a quote and three quotes had been received. A meeting had been held with each of the three providers on 27 April 2022 and a decision on which to appoint would be made by 29 April 2022. 6.4 Council of Governors’ Expenses Reimbursement Protocol The CoG expenses reimbursement protocol had been updated and reformatted and additional clarification had been added in a number of areas not previously included in the protocol. The protocol was required to approved by the Board in accordance with the Trust’s constitution. Clarification for governors was requested in relation to: • how costs for printing would be reimbursed; and • whether governors who had been issued with permits for staff car parks could continue to use these when attending CoG meetings at the main hospital site. Actions: KR would review the issue of printing costs and the parking arrangements at the Trust for when meetings resumed in person. 6.5 Consultation Regarding Timings of Council of Governors’ Meetings At the CoG meeting on 22 January 2022, it had been agreed that a survey of governors would be carried out to identify the preferred times of day for CoG meetings with a view to varying the times of future meetings. This followed the resignation of two staff governors who had been unable to regularly attend meetings of the CoG due to work commitments. Ten responses to the survey had been received. There was a slight preference expressed for meetings to be held at regular times, although no overall majority in favour of regular or varied meeting times. Most governors identified meetings held in the mornings or afternoons to be more convenient and meetings held in the 6 evenings were less convenient for most governors. The CoG was asked to consider: • whether they would like to hold some or all CoG meetings in the morning; • whether they would prefer to hold CoG working group meetings in person when meetings in person were able to resume or whether to continue holding these meetings virtually using Teams would be preferable in terms of securing good attendance; and • if CoG working group meetings were held in person would it most convenient to schedule these on the same day as CoG meetings so that all meetings would be held in person on the same day. Some governors felt virtual meetings made it possible for them to attend more regularly as travelling time was not required and it was noted that attendance at meetings had increased since the introduction of virtual meetings. Virtual meetings also had benefits in terms of reducing congestion on the hospital sites and contributed positively to the delivery of the Trust’s green plan. It was more beneficial to hold meetings in person where these could be combined with a visit to an area of the hospital. Decision: The CoG agreed to retain a mix of meetings in the mornings and afternoons and a combination of face-to-face and virtual meetings once face-to-face meetings could resume. 7 Membership Engagement and Governor Activity 7.1 Membership Engagement SD introduced the membership engagement report highlighting that: • since the last CoG meeting in January 2022 there had been regular engagement with members; • in March 2022 members were informed of the appointment of Jenni Douglas-Todd as new chair of the Trust from July 2022; • as demand for hospital services had increased during April 2022 members had been kept up to date with the latest position and how they could assist by sharing messages to ensure that those who need medical treatment used the most appropriate service; • the Connect newsletter was sent in February and April 2022, with the latter edition split into versions for different constituencies for public members and staff and included details of which governors represented their area and an interview with one of the elected governors; • emails had been sent to all members aged 18 to 30 directly inviting them to take part in a study comparing COVID-19 vaccine doses when used as a third dose at the end of January 2022 and to other members asking them to help share information about recruitment to the study; • targeted emails were sent to members under 30 years of age to publicise a University of Southampton study into the kind of voluntary work, community activities and informal work that young people may have been doing during the pandemic; • the Trust advertised a listening event regarding children and young people with a learning disability organised by our patient involvement team for members with a specific interest in children’s services; • in February 2022 an online survey was launched to help shape the future of the Trust’s membership programme and governors who had provided feedback on the survey prior to its launch were thanked for their support; • KR and SD had attended a listening lunch for carers in Southampton earlier in April 2022, which was organised by the experience of care team; • weekly governor updates including a summary of key staff briefing 7 messages continued to be sent; and • since the last CoG meeting on 26 January 2022, 19 new members had joined the Trust. Future plans included: • supporting the upcoming CoG election in four public constituencies and two staff constituencies; • planning and executing a virtual event for members focusing on research at the Trust in May 2022; • taking part in upcoming community events to promote UHS membership and communicate key Trust messages; and • producing an edition of Connect in June 2022. 7.2 Governors’ Nomination Committee Feedback Feedback from the GNC meeting on 26 April 2022 was provided earlier in the meeting. 7.3 Feedback from Strategy and Finance Working Group In the absence of TW, KR advised that the Strategy and Finance Working Group had met on 21 April 2022. Topics considered had included: • the operational plan 2022/23; • an overview of non-NHS activity; • an update on the annual report and accounts; the process of annual self-certification of the Trust's licence conditions; and • a review of the Strategy and Finance Working Group terms of reference. 7.4 Feedback from Patient and Staff Experience Working Group FQ advised that a meeting of the Patient and Staff Experience Working Group had been held on 20 April 2022. This had been a very interesting session with presentations of the Trust’s new people strategy, the results of the NHS staff survey 2021 and the NHS maternity survey 2021 results. A review of the Patient and Staff Experience Working Group terms of reference was also carried out. 7.5 Feedback from Membership and Engagement Working Group RP advised that a meeting of the Membership and Engagement Working Group had been held on 26 April 2022. The following areas had been covered at the meeting: • SD had attended to provide a membership update and feedback on events held since the last meeting and also provide information on future events; • proposals to introduce an appointed governor for students as part of the composition of the CoG; and • a review of the Membership and Engagement Working Group terms of reference. CR was planning to engage with constituents in the Isle of Wight and RP suggested that all governors be supplied with some paper copies of Trust membership application forms for distribution amongst their constituents. Action: SD would provide a supply of Trust membership application forms to KR for distribution to governors. 8 Any Other Business There was no other business. 8 9 Date of Next Meeting – 19 July 2022 To note the date of the next meeting. RP suggested the meeting was held at its usual time of 2pm, immediately following the separate meeting between the governors and NEDs. There being no further business, the meeting concluded. 9 4 Matters Arising/Summary of Agreed Actions 1 4 Summary of Agreed Actions.docx List of action items Agenda item Assigned to 13 July 2022 10:55 Deadline Status Council of Governors 27/04/2022 7.5 Feedback from Membership and Engagement Working Group 687. Issue of a supply of Trust membership forms for distribution by governors Karen Russell 20/07/2022 Complete Explanation action item RP suggested that governors could be issued with a few Trust membership forms for distribution to promote membership. It was agreed that KR would send a supply to each governor. Explanation Russell, Karen A supply of Trust membership forms were issued to governors on 10 May 2022 as agreed. Council of Governors 27/04/2022 6.4 Council of Governors' Expenses Reimbursement Protocol 686. Reimbursement of printing costs and availability of parking Karen Russell 20/07/2022 Complete Explanation action item RP asked whether governors could be reimbursed for printing papers at home. A further query was raised regarding the availability of parking when face to face meetings resumed. Explanation Russell, Karen As part of the UHS Green Plan and wider sustainability, we want to avoid any unnecessary printing and we would also like to avoid any governors having to incur printing costs when printing at home. To facilitate this, at face to face meetings there will be a free wi-fi connection and a paper copy of the agenda only will be provided. Supporting papers will be displayed on the screen in the meeting room where necessary to support the discussion. On any other occasion which governors are attending an interview or other event where paper copies of any information may be required, these can be printed and provided by the Trust on a more cost-effective basis. A full response was circulated to governors on 23 May 2022. 13 July 2022 10:55 With regard to the availability of parking when attending face to face meetings, KR has arranged with Travelwise to cordon off an area of one of the car parks for use by governors when attending CoG meetings and exit car passes will be provided free of charge for use at these meetings. In view of this governor parking permits will no longer be required. KR will circulate details of the car park which should be used in advance of the next face to face meeting. Council of Governors 31/03/2021 5.5 Amendment to the Trust's Constitution - CCG Merger 444. Review the Council of Governors' Composition Helen Potton/Karen Russell 19/10//2022 Pending Explanation action item A review of the Council of Governors' composition is to be carried out to check that it still remains appropriate. The review was presented to the CoG at the meeting on 21 July 2021. The CoG agreed that volunteers for a task and finish group would be sought to consider the composition of the CoG in more detail. If no volunteers were forthcoming it would be referred to the Membership and Engagement Working Group for further review. Explanation Russell, Karen Following discussions by the Membership and Engagement Working Group, proposals for a change to the composition of the CoG relating to the New Forest, Eastleigh and Test Valley, and Rest of England and Wales constituencies will be presented for approval at the CoG meeting on 20 July 2022. Suggestions regarding young governor representatives were discussed further at the Membership and Engagement Working Group meeting on 27 June 2022. Proposals are to include two young governors as full members of the CoG, one each from the University of Southampton and the UHS Young Adults Group. This will be considered in more detail by a sub group and proposals will then be presented to the CoG. Page 2 5.1 Chief Executive Officer's Performance Report 1 5.1i Report template UHS CoG July 2022.docx Report to the Council of Governors Title: Agenda item: Sponsor: Author: Date: Purpose Chief Executive Officer’s Performance Report 5.1 David French, Chief Executive Officer Jason Teoh, Director of Data and Analytics 20 July 2022 Assurance Approval or reassurance Ratification Information Y Issue to be addressed: Information about Trust performance supports the Council of Governors in their role. Response to the issue: This report is intended to inform the Council of Governors about aspects of the Trust’s performance. Implications: Risks: This report provides performance information relating to a broad range of Trust services and activities, there are no specific implications. This report is provided for the purpose of information. Summary: This report is provided for the purpose of information. Page 1 of 1 1 5.1ii Chief Executive's Performance Report Jul 2022 FINAL.docx UHS Council of Governors 20th July 2022 Chief Executive’s Performance Report 1. Purpose and Context The purpose of this report is to summarise the Trust’s performance against a range of key indicators. This report covers data from the period from March to May 2022, noting that performance in relation to some of the targets is reported further in arrears. Notable features of the period included: • An increase in the number of COVID-19 inpatients through the period as rates of infection increased across the country. There was also a corresponding increase in the number of hospital-acquired COVID-10 infections. • Extremely high volume of attendances to the Emergency Department, averaging 378 patients per day, an 18% increase on the same period the prior year. • A significant number of patients not meeting the criteria to reside (formerly medically optimised for discharge), usually between 180 – 200 patients, continuing to occupy hospital beds, restricting flexibility in our elective programmes. The number has been as high as 229. Such patients are typically waiting for care to be provided in the community to continue their recoveries or meet long term needs in their home setting. • Referral volumes have exceeded pre-pandemic levels, and despite an increase in hospital activity, the RTT waiting list continues to increase. So far in 2022, the waiting list has grown by 10%. • High numbers of referrals have also been seen for patients with suspected cancer, which have impacted our 2 week wait and 62 Day performance. However, for both metrics, we continue to benchmark in the upper quartile of our teaching hospital peers. • A longer-term trend in higher staff sickness absence continues to rise, with an underlying 0.6-1% of absences in any given week being related to COVID-19. Page 1 of 7 2. Safety Infection Control Clostridium Difficile infection MRSA Bacterium infection Target 95.0% ≥ 90.0% Mar 2022 Apr 2022 67.5% 70.4% 76.9% 79.5% May 2022 67.5% 77.3% Attendances to the main (Type 1) Emergency Department (ED) have continued to increase throughout this period, averaging 378 per day (up 18% on the same period the previous year). UHS four-hour performance has deteriorated; however, we continue to benchmark well against other trusts.. In the period of March to May 2022, UHS ranked in the top quartile of the 16 teaching hospitals that we benchmark against (Type 1 attendances). A related, national, issue is ambulance handover times. UHS continues to maintain timeliness in accepting the handover of patients from ambulance staff, despite challenges this may create within our own department on some occasions. We have maintained handover time between March to May 2022 (despite higher attendances). Referral to Treatment (RTT) % incomplete pathways within 18 weeks in month Total patients on a waiting list Target => 92% Mar 2022 67.7% 46,318 Apr 2022 66.4% 48,458 May 2022 68.1% 49,283 Since December 2021, the number of patients on the RTT waiting list has increased by 10%. Referrals have returned to, and are now exceeding, pre-pandemic levels. This means that despite UHS’s activity having increased, we continue to see growth within the waiting list. However, we have made good progress in reducing the longest waiting patients. At the end of May, we only had 10 patients who had waited over two years for treatment (four of which were patient related delays). By the end of June – in line with the NHS requirements – we will have no patients waiting over two years for treatment, apart for any patient requested delays. Cancer Urgent GP referrals seen in 2 weeks Breast symptomatic patients’ referral seen in 2 weeks Treatment started within 62 days of urgent GP referral Target => 93% => 93% => 85% Mar 2022 90.4% 63.6% 72.3% Apr 2022 87.2% 91.7% 74.7% May 2022 86.9% 100% 69.5% There has been improvement within our two week wait (2WW) capacity, particularly within our Breast service as additional consultants have started and the service has run multiple weekend sessions through 2022. There remain some challenges within the Gynaecology and Head & Neck tumour sites – mainly due to higher referrals and staffing challenges. However, despite these performance issues, we continue to benchmark in the top quartile for performance relative to our teaching hospital peers. As a result of referral and treatment challenges, our 62 day cancer treatment performance has been adversely impacted. This is partly due to higher referral volumes, alongside late tertiary referrals, but also highlights some challenges that we have within existing pathways. We are working with the Wessex Cancer Page 5 of 7 Alliance to review, and optimise, relevant cancer pathways. Despite the challenges, UHS continues to benchmark in the upper quartile compared to our peer teaching hospitals. 5. Finance The Trust has now submitted its annual accounts to NHS England and NHS Improvement for 2021/22 reporting a small surplus of £0.05 million from a revenue position of over £1.2 billion, once items deemed as “below the line”, such as impairments to the valuation of our fixed assets, were removed. This met the national minimum breakeven mandate required for NHS organisations. Supporting this delivery was the achievement of £15 million of efficiencies in year, which, although below previous years’ levels, was a significant achievement given the level of operational pressure. Operating income increased £160 million from the previous financial year with significant funding increases related to the UK Health Security Agency saliva mass testing programme contract and also increases in research and development income due predominantly to COVID-19 vaccine studies. Additionally, NHS income continued to grow both in line with funding settlements and inflationary awards together with service expansions and elective recovery funding. Spend increased in equal measure however, with pay spend increasing by £57 million from the previous year. The trusts capital programme for 2021/22 also closed on plan with delivery in full to capital departmental expenditure limits (CDEL). Spend totalled £65 million, including investment in new theatres, expanding our emergency department and expanding our ophthalmology capacity. The underlying financial position of the trust is however more challenging, with inflationary pressures particularly within energy costs, a continuation of covid spend mainly on staff sickness/absence backfill, and drugs cost growth in excess of block funding levels, all creating financial pressure. The trust has however submitted a breakeven plan for 2022/23 which is predicated on the delivery of cost improvement plans totalling £45m (4%). For April and May the YTD position is a £5m deficit which is £2.2m below planned levels as a deficit had been anticipated in earlier months of the year knowing that traction on the trusts savings programme would take time to establish. The gap to plan is mainly driven by covid costs greater than forecast in addition to slower than anticipated delivery of cost improvement plans. Increased focus is now being applied in this area to ensure financial improvement is delivered and the breakeven plan for the year can be achieved. Capital spend is on plan year-to-date however much of the spend is profiled to later months with wards developments, MRI replacements and theatres expansion all planned for the second half of the year. Page 6 of 7 6. Human Resources Indicator Target Staff FFT - % of staff who agree or strongly agree that they would recommend UHS as a place to work Staff recommending UHS as a place to receive care/treatment => 75.5% => 85.0% Q4 21/22 73.8% National Average (Acute / Acute + Community Trusts) Picker average 58.4% 59.2% 84.9% 66.9% 66.8% The national NHS Staff Survey 2021 opened from September to November 2021 inclusive. Results are sent to individual trusts January to March, with embargo lifted in March 2022. Staff Survey results are now aligned to the NHS People Promise themes. UHS had a response rate of 56.2% (6,985 staff), representing a 6% increase from 2020. UHS scored average or above average on all seven themes. Our aim is to continue to improve, strive to increase our scores where all scores are above average in 2022, and aim for being the “best” scoring wherever possible thereafter Indicator Turnover (internal target) Sickness absence 12 month rolling (internal target) Nursing Vacancies (Registered Nurse only in clinical wards) (internal target) Target <=12% <=3.4% <=15% Mar 2022 14.3% 4.5% 12.8% Apr 2022 15.8% 4.6% 13.0% May 2022 14.9% 4.7% 13.6% Primarily reasons for sickness included: Covid-related sickness (including long Covid); work-related stress; and MSK. There has also been a recent increase in short-term sicknesses. End. Page 7 of 7 6.1 Non-Executive Director Reappointment and Appointment of Deputy Chair 1 6.1a Non-Executive Director Reappointment and Appointment of Deputy Chair front sheet v2 updated.docx Report to the Council of Governors Title: Agenda item: Sponsor: Author: Date: Purpose Non-Executive Director Reappointment and Appointment of Deputy Chair 6.1 Jenni Douglas-Todd, Trust Chair Karen Flaherty, Associate Director of Corporate Affairs and Company Secretary Helen Potton, Interim Associate Director of Corporate Affairs and Company Secretary 20 July 2022 Assurance Approval or reassurance Y Ratification Information Issue to be addressed: Response to the issue: Implications: Risks: Summary: The first three year term of office as a non-executive director for Tim Peachey will come to an end on 30 September 2022. Non-executive directors are eligible for reappointment for a second three year term subject to reappointment by the Council of Governors. One of the roles of the Governors’ Nomination Committee is to make recommendations to the Council of Governors on the reappointment of non-executive directors. The constitution provides for the appointment of a deputy chair. Jane Bailey is the current deputy chair and has resigned from that role as at the end of July 2022. It is proposed that Tim Peachey is reappointed for a second three year term of office. The attached paper provides details of the outcome of appraisals, changes to commitments and ongoing independence and commitment to the role. In terms of the deputy chair position it is proposed that a recommendation is made to the Council of Governors at their meeting on 19 October 2022. The appointment and reappointment of non-executive directors is one of the statutory responsibilities of the Council of Governors role following recommendation by the Governors’ Nomination Committee. The appointment of the deputy chair is one of the responsibilities of the Council of Governors. 1. Failure to ensure an appropriate balance of executive and independent non-executive directors in accordance with the Trust’s Constitution and The NHS Foundation Trust Code of Governance. 2. Ensuring the appropriate balance of skills and experience among the non-executive directors on the Board. 3. Ensuring the effective functioning of the Board. The Council of Governors is asked to approve Tim Peachey’s reappointment as a non-executive director for a second three year term commencing on 1 October 2022 on the same terms and conditions as his current appointment. The Governors’ Nomination Committee will be Page 1 of 2 asked to review the proposed reappointment at its meeting in July 2022 and will provide its recommendation to the Council of Governors. The Council of Governors is asked to approve the recommendation to defer the appointment of a deputy chair to the meeting on 18 October 2022 following a recommendation made by the newly appointed chair. Page 2 of 2 1 6.1b NED Reappointment and Appointment of Deputy Chair paper v2 updated.docx Non-Executive Director Reappointment and Appointment of Deputy Chair 1 Non-Executive Director Reappointment Background In September 2019 the Council of Governors (CoG) appointed Tim Peachey as a nonexecutive director for an initial three year term commencing on 1 October 2019. Nonexecutive directors are eligible for reappointment for a second three year term subject to reappointment by the CoG. When considering the reappointment of a non-executive director, the Governors’ Nomination Committee and the CoG should consider: • the outcome of the non-executive director’s appraisals since appointment; • their other commitments and the time available for the role; and • independence. Annual appraisal Tim Peachey has been subject to satisfactory appraisal annually since his appointment in 2019. Governors have had the opportunity to contribute to the appraisal of the non-executive directors each year by providing feedback through the Lead Governor. The most recent appraisal was carried out in February 2022. Following appraisal, the then Chair, Peter Hollins, confirmed that: • following formal performance evaluation, Tim Peachey’s performance as a nonexecutive director continued to be effective and demonstrated his commitment to the role; and • he would have no hesitation in recommending Tim Peachey for reappointment to the role following the appraisal process. Other commitments Since his original appointment, Tim has ceased his role as clinical safety officer of Block Solutions Ltd and taken on the role of Health Advisory Board member at Palantir Technologies UK, Ltd. Tim currently performs the following roles in addition to his role as a NED for the Trust: • Director, TP-Medcon Ltd • Clinical Advisor, Bolt Partners Ltd • Associate - Mediator, Problem Resolution Ltd • Non-Executive Director and Chair of Quality Committee, Isle of Wight NHS Trust • Health Advisory Board member, Palantir Technologies UK, Ltd. Tim has indicated his willingness to be reappointed for a further three year term and confirmed that he continues to have the time to commit to the role. This has been demonstrated through his attendance at meetings, which was considered as part of the appraisal process. 1 Independence Non-executive directors should be independent in character and judgement. Tim Peachey was considered to meet the requirements for independence applicable to a non-executive director on appointment. In his performance as a member of the Board of Directors and Audit and Risk Committee, chair of the Quality Committee and as the non-executive Maternity Safety Champion, Tim has continued to demonstrate his independence and constructive challenge. Since his appointment Tim has been subject to annual fit and proper persons checks and declaration processes applicable to directors to confirm ongoing compliance with the requirements. Recommendation Subject to recommendation by the Governors’ Nomination Committee, the Council of Governors is asked to reappoint Tim Peachey as a non-executive director for a second three year term commencing on 1 October 2022 on the same terms and conditions as his current appointment, including the current annual fee of £14,000 as remuneration for the role and the fee of £2,000 for additional chairing responsibilities in respect of the Quality Committee. 2 Appointment of Deputy Chair Background The appointment of the Deputy Chair is made by the Council of Governors. The current postholder, Jane Bailey, has advised that she intends to step down from the role as at the end of July 2022. When considering the appointment of a new Deputy Chair it would be usual for the view of the Chair of the Trust to be taken into consideration and a recommendation for approval be made. Recommendation Following the recent appointment of Jenni Douglas-Todd to the position of Chair of the Trust, it is recommended that a paper would be presented to the Council of Governors on 19 October 2022 with a recommendation in relation to the appointment of a Deputy Chair. 2 6.2 Amendments to the Constitution 1 6.2a Amendments to Constitution - cover sheet v2 updated.doc Report to the Council of Governors Title: Agenda item: Sponsor: Author: Date: Purpose Issue to be addressed: Amendments to Constitution 6.2 Jenni Douglas-Todd, Trust Chair Karen Flaherty, Associate Director of Corporate Affairs and Company Secretary Helen Potton, Interim Associate Director of Corporate Affairs and Company Secretary 20 July 2022 Assurance Approval or reassurance Y Ratification Information Following a review of the composition of the council of governors of the Trust, the council of governors has agreed to alter the number of governors elected by the areas of the public constituency to ensure that these remain representative of those to whom the Trust provides services. Having reviewed the current areas of the public constituencies and the proportion of patients seen by the Trust from those areas, the following proposed changes have been agreed: • to reduce the number of governors representing the Rest of England by one governor; and • to increase the number of governors representing New Forest, Eastleigh and Test Valley by one governor. The council of governors has also agreed to maintain a representative on the council of governors from local commissioners as an appointed governor, following the transfer of functions from NHS Hampshire, Southampton and Isle of Wight Clinical Commissioning Group to NHS Hampshire and Isle of Wight Integrated Care Board taking effect on 1 July 2022. Other minor changes are proposed to be made to the current constitution identified as part of this review and to correct minor typographical and other errors. These changes include: • to reflect the transfer of functions from Monitor/NHS Improvement to NHS England from 1 July 2022; • to update the model election rules attached at annex 4 to the constitution to those published by NHS Providers in August 2014 (these have not yet been updated to reflect the transfer of functions from Monitor to NHS England, however references to Monitor should be read as referring to NHS England); • to remove appendix 4 to annex 8 as it duplicates provisions in paragraph 25 of the constitution, as amended, and the terms of reference for the governors’ nomination committee; • to remove references to registers in paragraph 35 that are no longer maintained, or required to be maintained, by the Trust; • to all
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Daratumumab
Description
Chemotherapy Protocol Myeloma Daratumumab Regimen • Myeloma – Daratumumab monotherapy Indication • Daratumumab monotherapy is recommended as an option for treating relapsed and refractory multiple myeloma in adults whose previous therapy included a proteasome inhibitor and an immunomodulator (‘imid) as a fourth line of treatment, that is, after 3 previous treatments. Toxicity Drug Daratumumab Adverse Effect Infusion related reactions, hypotension, headache, rash, urticaria, pruritus, nausea, vomiting, respiratory tract infections (including pneumonia), neutropenia, thrombocytopenia, anaemia, lymphopenia, peripheral neuropathy, diarrhoea, muscle spasms, fatigue, pyrexia and peripheral oedema, blood transfusion related events The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Monitoring Drugs • FBC, U&Es, Ca2+ and LFTs prior to day one of each cycle of treatment. • Paraprotein and / or light chains prior to each cycle. • All patients should be tested for hepatitis B virus (HBV) before initiating treatment with daratumumab. Those patients who test positive for HBV infection should be discussed with a consultation specialist in HBV prior to initiating treatment with daratumumab to plan monitoring requirements whilst on treatment. Patients should also be tested for hepatitis C, CMV and HIV at the same time. • Send a blood sample to transfusion and inform patient and transfusion laboratory that patient is due to commence daratumumab. Patient will require red cell phenotyping as cross match fails due to binding of daratumumab to red cells. • Regular monitoring of blood glucose is considered good practice due to dexamethasone use. Version 1.2 (December 2018) Page 1 of 13 Myeloma – Daratumumab Dose Modifications The dose modifications listed are for haematological, liver and renal function and drug specific toxicities only. Dose adjustments may be necessary for other toxicities as well. In principle all dose reductions due to adverse drug reactions should not be re-escalated in subsequent cycles without consultant approval. It is also a general rule for chemotherapy that if a third dose reduction is necessary treatment should be stopped. Please discuss all dose reductions / delays with the relevant consultant before prescribing, if appropriate. The approach may be different depending on the clinical circumstances. Haematological No dose reductions of daratumumab are recommended. Dose delay may be required to allow recovery of blood cell counts in the event of haematological toxicity. Always refer to the responsible consultant, as any dose delays will be dependent on clinical circumstances and treatment intent. Low counts can be a consequence of bone marrow infiltration as well as drug toxicity. Consider blood transfusion or the use of erythropoietin according to NICE TA323 if patient symptomatic of anaemia or where the haemoglobin is less than 8g/dL (80g/L). Consider growth factor support as an alternative to the options below, particularly where there is evidence of bone marrow suppression. To initiate a new cycle of daratumumab, the neutrophil count must be 1x109/L or greater and the platelet count must be 50x109/L or greater, unless the low counts are due to bone marrow infiltration with myeloma. In this situation the daratumumab may be administered at the discretion of the treating consultant haematologist with the appropriate blood product and growth factor support. Neutrophils (x109/L) Less than 0.5x109/L or febrile neutropenia (fever greater than or equal to 38.5°C and neutrophils less than 1) Platelets (x109/L) Less than 50x109/L Dose Modifications Interrupt daratumumab treatment and monitor FBC weekly. Once neutrophils recover to 1x109/L, resume daratumumab at a dose of 16mg/kg. Dose Modifications Interrupt daratumumab treatment and monitor FBC weekly. Once platelets recover to 50x109/L or greater resume daratumumab at a dose of 16mg/kg. Hepatic Impairment No formal studies of daratumumab in patients with hepatic impairment have been conducted. Based on population pharmacokinetic analysis no dosage adjustments are necessary for patients with hepatic impairment Renal Impairment No dosage adjustment is necessary for patients with pre-existing renal impairment Version 1.2 (December 2018) Page 2 of 13 Myeloma – Daratumumab Infusion related reactions (IRR) Infusion reactions are reported in approximately half of patients who receive daratumumab and may occur up to 48 hours after the infusion has finished. The majority of infusion related reactions, 46%, occur with the first infusion, 2% with the second infusion and 3% with subsequent infusions. Signs and symptoms include bronchospasm, hypoxia, dyspnoea, hypertension, respiratory symptoms such as cough, wheezing, larynx and throat tightness and irritation, laryngeal oedema, pulmonary oedema, nasal congestion and allergic rhinitis. For infusion reactions of any grade/severity, immediately interrupt the infusion and manage the symptoms. Management of infusion reactions may further require reduction in the rate of infusion, or treatment discontinuation as outlined below. IRR grade Grade 1-2 (mild to moderate) Grade 3 (severe) Grade 4 (life threatening) Dose modification Once symptoms resolve, resume the infusion at no more than half the rate at which the reaction occurred. If the patient does not experience any further reaction symptoms, infusion rate escalation may resume at increments and intervals as appropriate. If the intensity of the reaction decreases to ≤Grade 2, consider restarting the infusion at no more than half the rate at which the reaction occurred. If the patient does not experience additional symptoms, resume infusion rate escalation at increments and intervals as appropriate. Permanently discontinue treatment upon the third occurrence of a Grade 3 or greater reaction. Permanently discontinue treatment. Regimen 28 day cycle until disease progression or intolerance (12 cycles will be set in Aria) Cycles 1 and 2 Drug Daratumumab Dose 16mg/kg Days 1,8,15,22 Administration Intravenous infusion in 500ml sodium chloride 0.9% Cycles 3 to 6 Drug Daratumumab Dose 16mg/kg Days 1 and 15 Administration Intravenous infusion in 500ml sodium chloride 0.9% Version 1.2 (December 2018) Page 3 of 13 Myeloma – Daratumumab Cycles 7 onwards Drug Daratumumab Dose 16mg/kg Day Administration Intravenous infusion 1 in 500ml sodium chloride 0.9% Dose Information • Daratumumab will be prescribed in accordance with the national dose bands (20 NS). Administration Information • The rate of daratumumab administration varies and depends on infusion related reactions. In order to determine the rate of the second and ongoing infusions all reactions and the first reaction free infusion must be recorded in the ARIA journal. • Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an in-line, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC, PP or PE administration sets must be used. First infusion Second infusionb Subsequent infusionsc Final volume 500ml 500ml 500ml Initial rate (first hour) 25ml/hour 50ml/hour 100ml/hour Rate incrementa 25ml/hour every hour 50ml/hour every hour 50ml/hour every hour Maximum rate 100ml/hour 200ml/hour 200ml/hour a Consider the incremental escalation of the infusion rate only in the absence of infusion reactions with the previous infusion b Escalate only if the patient’s first infusion of daratumumab was well tolerated (defined by an absence of NCI-CTC grade 2 or greater infusion-related reactions during the first 3 hours). If the previous infusion was not well tolerated then instructions for the first infusion c Escalate only if the patient’s first 2 infusions of daratumumab were well tolerated (defined by an absence of NCI-CTC grade 1 or greater infusion-related reactions during a final infusion rate of greater than or equal to 100 ml/hr). If the previous infusion was not well tolerated, then instructions for the second infusion will be used. For guidance on infusion rates in the case of infusion related reactions. See the managing infusion reactions section above. Rapid Infusion Protocol Data from a prospective, single-center and open label safety study of an accelerated daratumumab infusion suggests that a rapid (90 minute) daratumumab infusion schedule is well tolerated and safe, when administered from the 3rd infusion onwards in patients who have tolerated the 500mL daratumumab infusion at the manufacturer recommended rates. • The rapid rate of infusion is currently unlicensed. Version 1.2 (December 2018) Page 4 of 13 Myeloma – Daratumumab Inclusion criteria for daratumumab rapid rate infusion • Patients on cycle 2 and onwards who have received and tolerated the previous 500mL daratumumab infusion at the standard manufacturer licensed rate without Grade 1 infusion related reactions. • Patients must demonstrate tolerability of a 500mL daratumumab infusion at the manufacturer recommended rates prior to receiving the accelerated infusion. • Daratumumab when used as monotherapy only • Patients who have given consent to rapid rate daratumumab infusion if required by the individual Trust Exclusion criteria for daratumumab rapid rate infusion • Previous greater than or equal to grade 3 infusion related toxicity with daratumumab • Infusion related reactions greater than or equal to grade 1 with the most recent daratumumab infusion given at the standard manufacturer licensed rate i.e. patients must have received and tolerated the previous 500mL daratumumab infusion at the standard manufacturer licensed rate without grade 1 or above infusion related reactions. • Patients whose most recent dose was prepared in the 1000mL dilution due to moderate or severe infusion related reactions. Patients must demonstrate tolerability of a 500mL daratumumab infusion at the manufacturer recommended rates prior to receiving the accelerated infusion. • Patients receiving daratumumab as part of a combination regimen • Cardiac amyloid patients • Patients receiving daratumumab as part of clinical trials (follow trial protocol) Rapid infusion rate Daratumumab prepared in 500mL NaCl 0.9% • Infuse 100mL of the daratumumab infusion (20%) of the dose over 30 minutes • Then infuse the remaining 400mL (80% of the dose) over 60 minutes (total infusion time 90 minutes). Monitoring • Check vital signs before the start of the infusion, every 15 minutes during the first 60 minutes of the infusion and at the end of the infusion • Monitor patient for adverse effects. For the first rapid rate infusion, observe patients in the Day Unit for 30 minutes after infusion completion to assess for delayed infusion related reactions. • Closer monitoring is required if the patient has a history of uncontrolled hypertension, pre-existing COPD, asthma or other respiratory comorbidities. These patients should be discussed with the consultant. Additional therapy • Consider allopurinol 300mg once a day for seven days for the first cycle only oral • No anti-emetics are required Version 1.2 (December 2018) Page 5 of 13 Myeloma – Daratumumab • Premedication required 1 to 3 hours before every infusion; - chlorphenamine 10mg intravenous - dexamethasone 20mg intravenous cycle 1 and cycle 2. This can be reduced to 10mg intravenous or oral from the third cycle onwards. - paracetamol 1000mg oral - montelukast 10mg oral for the first two cycles only and the first “fast infusion” if this does not occur on cycle two • Dexamethasone 4mg oral each morning for 2 days starting the day after each infusion • Consider anti-infective prophylaxis including; - aciclovir 400mg twice a day oral - co-trimoxazole 960mg once a day oral on Monday, Wednesday and Friday only - fluconazole 100mg once a day oral only if recurrent oral candidiasis • Bisphosphonates in accordance with local policies. • Mouthwashes according to local or national policy on the treatment of mucositis. • Gastric protection with a proton pump inhibitor or an H2 antagonist may be considered in patients considered at high risk of GI ulceration or bleed. • As required for the treatment of infusion related reactions for patients at high risk of respiratory complications; - sodium chloride 0.9% 500ml intravenous - salbutamol 2.5mg nebulised - hydrocortisone sodium succinate 100mg intravenous - chlorphenamine 10mg intravenous - paracetamol 1000mg oral - oxygen as required Additional Information • All instances of infusion related reaction must be recorded on ARIA. Daratumumab will continue to be administered at the cycle one rate until a reaction free infusion is noted. • Daratumumab interferes with indirect antiglobulin tests as it binds to CD38 on red blood carpusles (RBCs) and interferes with compatibility testing, including antibody screening and cross matching. Daratumumab interference mitigation methods include treating reagent RBCs with dithiothreitol (DTT) to disrupt daratumumab binding or other locally validated methods. Since the Kell blood group system is also sensitive to DTT treatment, Kell-negative units should be supplied after ruling out or identifying alloantibodies using DTT-treated RBCs. Alternatively, phenotyping or genotyping may also be considered. • Daratumumab may be detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for monitoring disease monoclonal immunoglobulins (M protein). This can lead to false positive SPE and IFE assay Version 1.2 (December 2018) Page 6 of 13 Myeloma – Daratumumab results for patients with IgG kappa myeloma protein impacting initial assessment of complete responses by International Myeloma Working Group (IMWG) criteria. In patients with persistent very good partial response, consider other methods to evaluate the depth of response. Coding • Procurement –X71.5 • Delivery – X72.1, X72.4 References 1. Janssen-Cilag Limited (16 Aug 2017). Darzalex 20mg/ml Summary of Product Characteristics. Electronic Medicines Compendium. Online at https://www.medicines.org.uk/emc/product/7250 , accessed 18 January 2018. 2. National Institute for Health and Care Excellence (2018). Daratumumab for multiple myeloma [TA10076]. London: National Institute for Health and Care Excellence. 3. Thames Valley Strategic Cancer Network Myeloma Group MM32 Daratumumab (Darzalex TM) Monotherapy Protocol version 1.3 July 2017. 4. 90 minute daratumumab infusion is safe in multiple myeloma. Leukemia. Hallie Barr et al. Accessed 27/11/18 https://doi.org/10.1038/s41375-018-0120-2. Version 1.2 (December 2018) Page 7 of 13 Myeloma – Daratumumab REGIMEN SUMMARY Daratumumab Cycle 1 Day 1, 8, 15, 22 1. Warning – Inform blood transfusion Administration Instructions Daratumumab interferes with indirect antiglobulin tests as it binds to CD38 on red blood carpusles (RBCs) and interferes with compatibility testing, including antibody screening and cross matching. Daratumumab interference mitigation methods include treating reagent RBCs with dithiothreitol (DTT) to disrupt daratumumab binding or other locally validated methods. Since the Kell blood group system is also sensitive to DTT treatment, Kell-negative units should be supplied after ruling out or identifying alloantibodies using DTT-treated RBCs. Alternatively, phenotyping or genotyping may also be considered. Daratumumab may be detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for monitoring disease monoclonal immunoglobulins (M protein). This can lead to false positive SPE and IFE assay results for patients with IgG kappa myeloma protein impacting initial assessment of complete responses by International Myeloma Working Group (IMWG) criteria. In patients with persistent very good partial response, consider other methods to evaluate the depth of response Please inform blood transfusion when a patient is prescribed daratumumab 2. Chlorphenamine 10mg intravenous 3. Dexamethasone 20mg intravenous Administration Instructions Administer 20mg intravenous or equivalent dose 4. Paracetamol 1000mg oral Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 5. Montelukast 10mg oral 6. Daratumumab 16mg/kg in 500ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of daratumumab administration varies and is dependant the occurance and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC, PP or PE administration sets must be used. 7. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 8. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 9. Paracetamol 1000mg oral when required for the relief of infusion related reactions 10. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions 11. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Take home medicines (day 1 only) 12. Dexamethasone 4mg on days 2, 3, 9, 10, 16, 17, 23 and 24 oral Administration Information Version 1.2 (December 2018) Page 8 of 13 Myeloma – Daratumumab Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice. 13. Allopurinol 300mg once a day for 7 days oral Administration information Take in the morning with food and plenty of water. This should be supplied for the first cycle only. 14. Aciclovir 400mg twice a day for 28 days oral Administration Instructions Please supply 28 days or an original pack if appropriate. 15. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 28 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 28 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice. 16. Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - esomeprazole 20mg once a day oral - omeprazole 20mg once a day oral - lansoprazole 15mg once a day oral - pantoprazole 20mg once a day oral - rabeprazole 20mg once a day oral - cimetidine 400mg twice a day oral - famotidine 20mg once a day oral - nizatidine 150mg twice a day oral - ranitidine 150mg twice a day oral Please supply 28 days or the nearest original pack size. Cycle 2 days 1, 8, 15, 22 17. Chlorphenamine 10mg intravenous 18. Dexamethasone 20mg intravenous Administration Instructions Administer 20mg intravenous or equivalent dose 19. Paracetamol 1000mg oral Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 20. Montelukast 10mg oral 21. Daratumumab 16mg/kg in 500ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of daratumumab administration varies and is dependant the occurance and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC, PP or PE administration sets must be used. 22. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 23. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 24. Paracetamol 1000mg oral when required for the relief of infusion related reactions Version 1.2 (December 2018) Page 9 of 13 Myeloma – Daratumumab 25. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions 26. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Take home medicines (day 1 only) 27. Dexamethasone 4mg on days 2, 3, 9, 10, 16, 17, 23 and 24 oral Administration Information Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice. 28. Aciclovir 400mg twice a day for 28 days oral Administration Instructions Please supply 28 days or an original pack if appropriate. 29. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 28 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 28 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice. 30. Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - esomeprazole 20mg once a day oral - omeprazole 20mg once a day oral - lansoprazole 15mg once a day oral - pantoprazole 20mg once a day oral - rabeprazole 20mg once a day oral - cimetidine 400mg twice a day oral - famotidine 20mg once a day oral - nizatidine 150mg twice a day oral - ranitidine 150mg twice a day oral Please supply 28 days or the nearest original pack size. Cycle 3, 4, 5, 6 days 1, 15 31. Chlorphenamine 10mg intravenous 32. Dexamethasone 10mg intravenous Administration Instructions Administer 10mg intravenous or equivalent dose 33. Paracetamol 1000mg oral Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 34. Daratumumab 16mg/kg in 500ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of daratumumab administration varies and is dependant the occurance and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC, PP or PE administration sets must be used. 35. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions Version 1.2 (December 2018) Page 10 of 13 Myeloma – Daratumumab 36. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 37. Paracetamol 1000mg oral when required for the relief of infusion related reactions 38. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions 39. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Take home medicines (day 1 only) 40. Dexamethasone 4mg on days 2, 3, 16 and 17 oral Administration Information Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice. 41. Aciclovir 400mg twice a day for 28 days oral Administration Instructions Please supply 28 days or an original pack if appropriate. 42. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 28 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 28 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice. 43. Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - esomeprazole 20mg once a day oral - omeprazole 20mg once a day oral - lansoprazole 15mg once a day oral - pantoprazole 20mg once a day oral - rabeprazole 20mg once a day oral - cimetidine 400mg twice a day oral - famotidine 20mg once a day oral - nizatidine 150mg twice a day oral - ranitidine 150mg twice a day oral Please supply 28 days or the nearest original pack size. Cycle 7 day 1 onwards 44. Chlorphenamine 10mg intravenous 45. Dexamethasone 10mg intravenous Administration Instructions Administer 10mg intravenous or equivalent dose 46. Paracetamol 1000mg oral Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 47. Daratumumab 16mg/kg in 500ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of daratumumab administration varies and is dependant the occurance and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC, PP or PE administration sets must be used. Version 1.2 (December 2018) Page 11 of 13 Myeloma – Daratumumab 48. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 49. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 50. Paracetamol 1000mg oral when required for the relief of infusion related reactions 51. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions 52. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Take home medicines (day 1 only) 53. Dexamethasone 4mg on days 2, 3 oral Administration Information Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice. 54. Aciclovir 400mg twice a day for 28 days oral Administration Instructions Please supply 28 days or an original pack if appropriate. 55. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 28 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 28 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice. 56. Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - esomeprazole 20mg once a day oral - omeprazole 20mg once a day oral - lansoprazole 15mg once a day oral - pantoprazole 20mg once a day oral - rabeprazole 20mg once a day oral - cimetidine 400mg twice a day oral - famotidine 20mg once a day oral - nizatidine 150mg twice a day oral - ranitidine 150mg twice a day oral Please supply 28 days or the nearest original pack size. Version 1.2 (December 2018) Page 12 of 13 Myeloma – Daratumumab DOCUMENT CONTROL Version Date Amendment Written By Approved By Rapid infusion protocol added 1.2 December 2018 Additional tests prior to starting Nanda Basker Pharmacist Dr Deborah Wright Pharmacist treatment National dose bands added 1.1 August 2018 Daratumumab administration instructions updated. Dr Deborah Wright Pharmacist Donna Kimber Pharmacy Technician Disclaimer updated Harriet Launders 1 January 2018 None Pharmacist Dr Deborah Wright Dr Mathew Jenner Consultant Haematologist Pharmacist This chemotherapy protocol has been developed as part of the chemotherapy electronic prescribing project. This was and remains a collaborative project that originated from the former CSCCN. These documents have been approved on behalf of the following Trusts; Hampshire Hospitals NHS Foundation Trust NHS Isle of Wight Portsmouth Hospitals NHS Trust Salisbury NHS Foundation Trust University Hospital Southampton NHS Foundation Trust Western Sussex Hospitals NHS Foundation Trust All actions have been taken to ensure these protocols are correct. However, no responsibility can be taken for errors that occur as a result of following these guidelines. These protocols should be used in conjunction with other references such as the Summary of Product Characteristics and relevant published papers. Version 1.2 (December 2018) Page 13 of 13 Myeloma – Daratumumab
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/Media/UHS-website-2019/Docs/Chemotherapy-SOPs1/Myeloma/Daratumumab.pdf
Virtual consultation, actual peril
Description
A court considers whether a virtual consultation is sufficient for assessing a patient's mental health.
Url
/HealthProfessionals/Clinical-law-updates/Virtual-consultation-actual-peril.aspx
IPD-Dexamethasone-Isatuximab-Pomalidomide
Description
Chemotherapy Protocol Myeloma Isatuximab-Dexamethasone (40)-Pomalidomide Regimen • Myeloma – Isatuximab-Dexamethasone (40)-Pomalidomide Indication • Isatuximab is indicated where; - the patient has a diagnosis of multiple myeloma - the patient has received 3 and only 3 prior lines of treatment and that the numbering of a line of treatment is in accordance with the International Myeloma Workshop Consensus recommendations for the uniform reporting of clinical trials (http://doi.org/10.1182/blood-2010-10-299487). A line of therapy is defined as one or more cycles of a planned treatment program. This may consist of one or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner (eg induction chemotherapy/chemotherapies if followed by stem cell transplantation is considered to be 1 line of therapy). A new line of therapy starts when a planned course of therapy is modified to include other treatment agents (alone or in combination) as a result of disease progression, relapse or toxicity. A new line of therapy also starts when a planned period of observation off therapy is interrupted by a need for additional treatment for the disease. Note: the use of isatuximab in combination with pomalidomide and dexamethasone in patients who have had 3 and only 3 prior lines of therapy has been chosen by Sanofi for this EAMS scheme. The use of isatuximab in combination with pomalidomide and dexamethasone in the 1-prior, 2-prior, 4-prior and > 4-prior patient groups is not permitted within this EAMS scheme. - the patient has received prior treatment with at least 2 consecutive cycles of lenalidomide given alone or in combination and has failed treatment with lenalidomide on account of disease progression, refractory disease or intolerance - the patient has received prior treatment with at least 2 consecutive cycles of a proteasome inhibitor (eg bortezomib or carfilzomib or ixazomib) given alone or in combination and has failed treatment with a proteasome inhibitor on account of disease progression, refractory disease or intolerance - the patient has responded to at least one previous line of treatment ie the patient does not have primary refractory myeloma - the patient was refractory to the last line of therapy ie there was progression on or within 60 days of the end of the last line of active anti-myeloma systemic therapy. - the patient either has had no previous therapy with any anti-CD38 antibody (eg daratumumab) or if there has been previous treatment with an anti-CD38 Version 2 (February 2024) Page 1 of 18 Myeloma – Isatuximab- Dexamethasone (40)-Pomalidomide antibody then the patient did not progress whilst still receiving the anti-CD38 therapy or did not progress within 60 days of the last infusion of anti-CD38 treatment. - isatuximab is only to be used in combination with pomalidomide and dexamethasone and not with any other active systemic agents for myeloma - isatuximab is only to be used in combination with pomalidomide and dexamethasone and not with any other active systemic agents for myeloma - the patient has an ECOG performance status of 0 or 1 or 2 - a formal medical review as to whether treatment with isatuximab should continue or not will be scheduled to occur at least by the end of the first 8 weeks of treatment • This protocol with a dose of dexamethasone of 40mg is recommended for those aged 75 years and below. Reduce dose to 20mg (or IV dose equivalent) in patients over 75 years. Version 2 (February 2024) Page 2 of 18 Myeloma – Isatuximab- Dexamethasone (40)-Pomalidomide Toxicity Drug Adverse Effect Infusion related reactions: dyspnoea, hypertension and bronchospasm. Diarrhoea, nausea, vomiting, upper respiratory tract infections, pneumonia, neutropenia, weight decrease. Isatuximab Istuximab interferes with indirect antiglobulin tests as it binds to CD38 on red blood corpuscles (RBCs) and interferes with compatibility testing, including antibody screening and cross matching. Isatuximab interference mitigation methods include treating reagent RBCs with dithiothreitol (DTT) to disrupt isatuximab binding or other locally validated methods. Since the Kell blood group system is also sensitive to DTT treatment, Kellnegative units should be supplied after ruling out or identifying allo-antibodies using DTT-treated RBCs. Alternatively, phenotyping or genotyping may also be considered. Isatuximab may be detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for monitoring disease monoclonal immunoglobulins (M protein). This can lead to false positive SPE and IFE assay results for patients with IgG kappa myeloma protein impacting initial assessment of complete responses by International Myeloma Working Group (IMWG) criteria. In patients with persistent very good partial response, consider other methods to evaluate the depth of response Pomalidomide Dexamethasone Please inform blood transfusion when a patient is prescribed isatuximab – before first administration in cycle 1. Teratogenicity, cardiac failure, atrial fibrillation, thromboembolic events, interstitial lung disease, pneumonia, neutropenia, thrombocytopenia, leucopenia, anaemia, decreased appetite, dyspnoea, cough, gastrointestinal disturbance, bone pain, muscle spasm, fatigue, pyrexia, peripheral oedema, renal failure, peripheral neuropathy, skin reactions. Weight gain, gastrointestinal disturbances, hyperglycaemia, CNS disturbances, cushingoid changes, glucose intolerance. The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics and EAMS treatment protocol for full details. Monitoring Drugs • FBC at baseline and day 15 in cycle 1 (the full cycle of pomalidomide may be dispensed on day 1). Thereafter monitor prior to each cycle. • U&Es, Ca2+ and LFTs prior to day one of each cycle of treatment. • Paraprotein and/or light chains prior to each cycle. Version 2 (February 2024) Page 3 of 18 Myeloma – Isatuximab- Dexamethasone (40)-Pomalidomide • For all women of childbearing potential a negative pregnancy test must be obtained within the 3 days prior to starting pomalidomide. The test must be repeated every 4 weeks (every 2 weeks in women with irregular menstrual cycles) with the final test 4 weeks after the last dose of pomalidomide. • All patients should be tested for HIV, hepatitis A, B and C before initiating treatment. Active infection is an exclusion criteria in the EAMS scheme for isatuximab. Those patients who test positive for hepatitis B virus (HBV) without active infection should be discussed with a consultant specialist in HBV prior to initiating treatment with pomalidomide. Pomalidomide in combination with dexamethasone should be used cautiously in patients previously infected with HBV, including patients who are antiHBc positive but HBsAg negative. These patients should be closely monitored for signs and symptoms of active HBV infection throughout therapy. • Perform a venous thromboembolism (VTE) risk assessment prior to starting treatment. Prescribe thromboprophylaxis. • Regular monitoring of blood glucose is considered good practice due to use of steroids. Dose Modifications The dose modifications listed are for haematological, liver and renal function and drug specific toxicities only. Dose adjustments may be necessary for other toxicities as well. In principle all dose reductions due to adverse drug reactions should not be re-escalated in subsequent cycles without consultant approval. It is also a general rule for chemotherapy that if a third dose reduction is necessary treatment should be stopped. Please discuss all dose reductions / delays with the relevant consultant before prescribing, if appropriate. The approach may be different depending on the clinical circumstances. Haematological Dose modifications for haematological toxicity in the table below are for general guidance only. Always refer to the responsible consultant as any dose reductions or delays will be dependent on clinical circumstances and treatment intent. Low counts can be a consequence of bone marrow infiltration as well as drug toxicity. Consider blood transfusion or the use of erythropoietin according to NICE TA323 if patient symptomatic of anaemia or where the haemoglobin is less than 8g/dL (80g/L). Consider growth factor support as an alternative to the options below, particularly where there is evidence of bone marrow suppression. To initiate a new cycle of pomalidomide, the neutrophil count should be 1x109/L or greater and the platelet count must be 50x109/L or greater. It is acceptable to use growth factors in order to achieve this apart from prior to first cycle. Version 2 (February 2024) Page 4 of 18 Myeloma – Isatuximab- Dexamethasone (40)-Pomalidomide Neutrophils (x109/L) Less than 1.0x109/L Less than 0.5x109/L or febrile neutropenia (fever greater than or equal to 38.5°C and neutrophils less than1) Dose Modifications Exclusion criteria from EAMS is neutrophil count less than 1.0x109/L at baseline. NOTE growth factors cannot be used to reach this level prior to cycle 1. Delay isatuximab treatment until neutrophil count improves to at least 1.0x109/L. The use of growth factors is permitted within local guidelines. See below of isatuximab and interrupt pomalidomide treatment and monitor FBC weekly. Once neutrophils recover to 1x109/L, resume pomalidomide at a dose of 3mg once a day. For each subsequent drop to less than 0.5x109/L Platelets (x109/L) Less than 75x109/L Less than 25x109/L Interrupt pomalidomide treatment and monitor FBC weekly, once neutrophils recover to 1x109/L or greater then resume pomalidomide at 1mg less than previous dose. Dose Modifications Exclusion criteria for isatuximab from EAMS is platelets less than 75x 109/L if less than 50% of bone marrow (BM) nucleated cells are plasma cells and 30x109/L if more than 50% of BM nucleated cells are plasma cells at baseline. Interrupt pomalidomide treatment and monitor FBC weekly. Once platelets recover to 50x109/L or greater resume pomalidomide at a dose of 3mg once a day. For each subsequent drop to Interrupt pomalidomide and monitor FBC weekly and once less than 25x109/L platelets recover to 50x109/L, resume pomalidomide at 1mg less than previous dose. Hepatic Impairment Patients with serum total bilirubin greater than 2mg/dL were excluded from clinical studies. Hepatic impairment has a modest effect on the pharmacokinetics of pomalidomide. No adjustment of the starting dose of pomalidomide is required for patients with hepatic impairment as defined by the Child-Pugh criteria. However, patients with hepatic impairment should be carefully monitored for adverse reactions and dose reduction or interruption of pomalidomide should be used as needed. However, as markedly elevated levels of alanine aminotransferase and bilirubin have been observed in patients treated with pomalidomide together with cases of hepatitis that resulted in treatment discontinuation, regular monitoring of liver function is recommended for the first 6 months of treatment with pomalidomide and as clinically indicated thereafter. Drug Bilirubin μmol/L Isatuximab Less than 2 times ULN AST/ALT units/L Less than 3 times ULN Dose (% of original dose) These are maximum levels permitted at baseline for inclusion in isatuximab in EAMS. No ongoing dose adjustments described. No dose adjustment is recommended in patients with mild hepatic impairment. Data in patients with moderate and severe hepatic impairment are limited, but there is no evidence to suggest that dose adjustment is required in these patients. Version 2 (February 2024) Page 5 of 18 Myeloma – Isatuximab- Dexamethasone (40)-Pomalidomide Renal Impairment No dose adjustment of pomalidomide is required for patients with renal impairment. Where patients are receiving haemodialysis, the pomalidomide dose should be taken following haemodialysis. No dose adjustment for isatuximab is recommended for patients with mild to moderate renal impairment. Pomalidomide Cardiac Failure Cardiac failure is a known common adverse reaction associated with pomalidomide treatment (ie occurs in between 1/10 and 1/100 patients who take pomalidomide). In most cases, this side effect occurs in patients with cardiac disease or cardiac risk factors and within six months of starting pomalidomide. Pomalidomide can cause atrial fibrillation, which may precipitate cardiac failure. Monitor for signs and symptoms of cardiac impairment. Interstitial Lung Disease Intersitial lung disease (ILD), including cases of pneumonitis, have been observed with pomalidomide. Careful assessment of patients with an acute onset or unexplained worsening of pulmonary symptoms should be performed to exclude ILD. Pomalidomide should be interrupted during investigation of these symptoms and if ILD is confirmed, appropriate treatment should be initiated. Pomalidomide should only be resumed after a thorough evaluation of the benefits and the risks. Pregnancy As pomalidomide is structurally related to thalidomide a teratogenic effect is expected, therefore, it must not be taken during pregnancy. All women of child bearing potential (even if they have amenorrhoea) must use one effective method of pregnancy prevention at least 4 weeks before therapy, during therapy and even in the case of dose interruptions, and for at least a further 4 weeks after stopping therapy. Additionally a negative pregnancy test is required prior to commencing each cycle of therapy. Men are required to undertake to use a barrier method of contraception. The conditions of the Celgene Pregnancy Prevention Programme must be fulfilled for all patients unless there is reliable evidence that the patient does not have childbearing potential. Skin Pomalidomide interruption or discontinuation should be considered for WHO grade 2-3 skin rash. Pomalidomide must be discontinued for angioedema, WHO grade 4 rash, exfoliative or bullous rash, or if Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN) or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is suspected, and should not be resumed following discontinuation from these reactions. Venous Thromboembolism (VTE) Patients receiving pomalidomide in combination with dexamethasone have developed venous thromboembolic events (predominantly deep vein thrombosis and pulmonary Version 2 (February 2024) Page 6 of 18 Myeloma – Isatuximab- Dexamethasone (40)-Pomalidomide embolism) and arterial thrombotic events (myocardial infarction and cerebrovascular accident). Appropriate VTE prophylaxis is recommended. All patients should receive aspirin unless contra-indicated. Patients deemed to be at high risk of VTE should receive a low molecular weight heparin. The duration of thromboprophylaxis remains unclear but guided by risk factors such as active disease (e.g. for the first 4 to 6 months of treatment until disease control achieved) and de-escalated or discontinued unless there are ongoing significant risk factors. If patients are treated with a low molecular weight heparin consider switching patients to aspirin after six cycles of therapy or after maximum response is achieved. A high index of suspicion for venous thromboembolism should always be maintained. If a venous thrombosis or embolism NCI-CTC grade 3 or above occurs then stop treatment and start full anticoagulation. Pomalidomide may be restarted at the clinician’s discretion, once the patient is fully anti-coagulated. Modifiable risk factors for thromboembolic events should be managed wherever possible to reduce the risk of VTE (e.g. smoking cessation; control of hypertension and hyperlipidaemia). Medicines that may increase the risk of thromboembolism, such as oestrogens and erythropoietic agents, should be used with caution during pomalidomide treatment. For all other NCI-CTCAE grade 3 or 4 adverse reactions, judged to be related to pomalidomide, stop treatment. Restart treatment when the adverse reaction has resolved to NCI-CTC grade 2 or below at 1 mg less than the previous dose, or at the consultants discretion. Dexamethasone Dose Level 3 (starting) 2 1 Dose 40mg 20mg 10mg If recovery from toxicities is prolonged beyond 14 days, then the dose of dexamethasone will be decreased by one dose level. Version 2 (February 2024) Page 7 of 18 Myeloma – Isatuximab- Dexamethasone (40)-Pomalidomide Toxicity Grade (NCI-CTC) Dose modification Dyspepsia 1-2 3 or above Oedema 3 or above Confusion or mood alteration 2 or above Muscle weakness 2 or above Hyperglycaemia 3 or above Acute pancreatitis Other 3 or above Maintain dose and treat with histamine (H2) antagonist or proton pump inhibitor. Decrease by one dose level if symptoms persist. Interrupt dose until symptoms are controlled. Add H2 blocker or proton pump inhibitor and decrease one dose level when dose restarted. Use diuretics as needed and decrease dose by one dose level. Interrupt dose until symptoms resolve. When dose restarted decrease dose by one dose level. Interrupt dose until the muscle weakness is grade 1 or below. Restart with dose decreased by one level. Decrease dose by one dose level. Treat with insulin or oral hypoglycaemic agents as needed Discontinue patient from dexamethasone treatment regimen. Stop dexamethasone dosing until adverse event resolves to grade 2 or below. Resume with dose reduced by one level. Regimen 28 day cycle until disease progression or intolerance (12 cycles will be set in Aria) Cycle 1 Drug Isatuximab Dose 10mg/kg Pomalidomide 4mg once a day Days 1,8,15 and 22 1-21 (inclusive) Administration Intravenous infusion in 250ml sodium chloride 0.9% at a variable rate Oral Oral Dexamethasone 40mg Version 2 (February 2024) 1, 8 15 and 22 Reduce dose to 20mg (or iv dose equivalent) in over 75yrs Page 8 of 18 Myeloma – Isatuximab- Dexamethasone (40)-Pomalidomide Cycle 2 onwards Drug Isatuximab Dose 10mg/kg Pomalidomide 4mg once a day Days 1 and 15 1-21 (inclusive) Administration Intravenous infusion in 250ml sodium chloride 0.9%at a variable rate Oral Oral Dexamethasone 40mg 1, 8 15 and 22 Reduce dose to 20mg (or iv dose equivalent) in over 75yrs Dose Information • The dose of dexamethasone should be reduced to 20mg in those over 75 years of age. • Dexamethasone is available as 500microgram, 2mg and 4mg tablets and as a 2mg/5ml oral liquid. • Isatuximab will be dose banded in accordance with national dose banding • Pomalidomide is available as 1mg, 2mg, 3mg and 4mg hard capsules. Administration Information • Dexamethasone should be taken in the morning with or immediately after food. • Pomalidomide should be taken at the same time each day. The capsules should be swallowed whole, preferably with water, with or without food and not be opened, broken or chewed. • Pomalidomide can cause drowsiness it may be advisable to take it at night. • If a dose of pomalidomide is forgotten on one day, the normal prescribed dose should be taken the next day. Patients should not adjust the dose to make up for missing a dose on previous days. • It is recommended to press only on one end of the pomalidomide capsule to remove it from the blister thereby reducing the risk of capsule deformation or breakage. • All prescriptions for pomalidomide must be accompanied by a prescription authorisation form (PAF). • The rate of isatuximab administration varies and depends on infusion related reactions. In order to determine the rate of the second and ongoing infusions all reactions and the first reaction free infusion must be recorded in the ARIA journal. • Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an in-line, sterile, non-pyrogenic, low protein-binding Version 2 (February 2024) Page 9 of 18 Myeloma – Isatuximab- Dexamethasone (40)-Pomalidomide polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC or PE administration sets must be used. First infusion Final volume 250ml Second infusion 250mL Subsequent infusionsa 250ml Initial rate (first hour) 25mL/hour 50mL/hour 200mL/hour Rate incrementa If absence of infusion reaction for 60 minutes increase by 25mL/hour every 30 minutes 50mL and hour for 30 minutes then increase by 100mL/hour Maximum rate 150mL/hour 200mL/hour 200mL/hour a Consider the incremental escalation of the infusion rate only in the absence of infusion reactions with the previous infusion Administration adjustments should be made if patients experience infusion reactions. In patients who experience Grade 2 (moderate) infusion reactions, a temporary interruption in the infusion should be considered and additional symptomatic medicinal products can be administered. After improvement to grade ≤1 (mild), isatuximab infusion may be resumed at half of the initial infusion rate under close monitoring and supportive care, as needed. If symptoms do not recur after 30 minutes, the infusion rate may be increased to the initial rate, and then increased incrementally, as shown in the table above. If symptoms do not resolve rapidly or do not improve to Grade ≤1 after interruption of isatuximab infusion, recur after initial improvement with appropriate medicinal products, or require hospitalization or are life-threatening (Grade ≥3), treatment with isatuximab should be permanently discontinued and additional supportive therapy should be administered, as needed. Check vital signs before the start of the infusion, every 15 minutes during the first 60 minutes of the infusion and at the end of the infusion for all isatuximab infusions. Additional therapy • Thromboprophylaxis, the choice depending on risk factors and duration of therapy. Low molecular weight heparin is preferred above aspirin unless there are other clinical reasons to guide thromboprophylaxis. • Allopurinol 300mg once a day for seven days for the first cycle only oral • Premedication required 15 – 60 minutes before every isatuximab infusion: - dexamethasone – see regimen for dose details - chlorphenamine 10mg intravenous - omeprazole 20mg oral - paracetamol 1000mg oral Version 2 (February 2024) Page 10 of 18 Myeloma – Isatuximab- Dexamethasone (40)-Pomalidomide • Consider anti-infective prophylaxis including; - aciclovir 400mg twice a day oral - co-trimoxazole 960mg once a day oral on Monday, Wednesday and Friday only • Bisphosphonates and calcium/vitamin D in accordance with local policies. • Mouthwashes according to local or national policy on the treatment of mucositis. • Gastric protection with a proton pump inhibitor or a H2 antagonist may be considered in patients considered at high risk of GI ulceration or bleed. • As required for the treatment of infusion related reactions for patients at high risk of respiratory complications; - sodium chloride 0.9% 500ml intravenous - salbutamol 2.5mg nebulised - hydrocortisone sodium succinate 100mg intravenous - chlorphenamine 10mg intravenous - paracetamol 1000mg oral - oxygen as required Additional Information • The National Patient Safety Alert on oral chemotherapy (NPSA/2008/RRR001) must be followed in relation to pomalidomide. • It must be made clear to all staff, including those in the community, that pomalidomide should only be prescribed under the supervision of a consultant haematologist. • Patients should be assessed for suitability for oral chemotherapy prior to starting treatment. • For all patients taking pomalidomide; the patient, prescriber and supplying pharmacy must comply with the Celgene pregnancy prevention programme (PPP). • If strong inhibitors of CYP1A2 (e.g. ciprofloxacin and fluvoxamine) are coadministered with pomalidomide, reduce the dose of pomalidomide by 50%. • All instances of infusion related reaction must be recorded on ARIA. Isatuximab will continue to be administered at the cycle one rate until a reaction free infusion is noted. • Isatuximab interferes with indirect antiglobulin tests as it binds to CD38 on red blood corpuscles (RBCs) and interferes with compatibility testing, including antibody screening and cross matching. Isatuximab interference mitigation methods include treating reagent RBCs with dithiothreitol (DTT) to disrupt isatuximab binding or other locally validated methods. Since the Kell blood group system is also sensitive to DTT treatment, Kell-negative units should be supplied after ruling out or identifying alloantibodies using DTT-treated RBCs. Alternatively, phenotyping or genotyping may also be considered. Version 2 (February 2024) Page 11 of 18 Myeloma – Isatuximab- Dexamethasone (40)-Pomalidomide • Isatuximab may be detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for monitoring disease monoclonal immunoglobulins (M protein). This can lead to false positive SPE and IFE assay results for patients with IgG kappa myeloma protein impacting initial assessment of complete responses by International Myeloma Working Group (IMWG) criteria. In patients with persistent very good partial response, consider other methods to evaluate the depth of response. Coding • Procurement – X71.5 • Delivery – X72.1 References 1. Celgene Limited (2016). Imnovid 4mg Summary of Product Characteristics. Electronic Medicines Compendium. Online at http://www.medicines.org.uk/emc/medicine/29475, accessed 25 January 2017. 2. National Institute for Health and Care Excellence (2017). Pomalidomide for multiple myeloma previously treated with lenalidomide and bortezomib. [TA427]. London: National Institute for Health and Care Excellence. 3. Celgene Limited (2013). Imnovid (Pomalidomide) Healthcare Professionals Information Pack UK Version 1.0. 4. Dimopoulos MA, Palumbo A, Corrodini P et al. Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010): a phase 3b study in refractory multiple myeloma. Blood (2016); 128 (4): 497-503. Version 2 (February 2024) Page 12 of 18 Myeloma – Isatuximab- Dexamethasone (40)-Pomalidomide REGIMEN SUMMARY Isatuximab-Dexamethasone (40)-Pomalidomide Cycle 1 Day 1 1. Warning – Check blood transfusion status Administration Instructions Patients treated with isatuximab carry a lifelong risk of transfusion associated graft versus host disease. Where blood products are required these patients must receive ONLY IRRADIATED BLOOD PRODUCTS for life. Ensure transfusion departments are notified and the patient has been issued with an alert card to carry at all times. 1. Chlorphenamine 10mg intravenous Administration Instructions Administer 15 – 60 minutes prior to Isatuximab 2. Warning – Dexamethasone Dose in Elderly Administration Instructions In those aged over 75 years reduce the dose of dexamethasone to 20mg once a day orally or equivalent intravenous dose 3. Dexamethasone 40mg oral Administration Instructions Administer 15 – 60 minutes prior to Isatuximab Administer 40mg once a day orally. For those unable to tolerate the oral route this can be administered at an equivalent intravenous dose. Reduce dose to 20mg orally or intravenous equivalent if the patient is over 75 years old. 4. Paracetamol 1000mg oral Administration Instructions Administer 15 – 60 minutes prior to Isatuximab Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 5. Omeprazole 20mg Oral Administration Instructions Administer 15 – 60 minutes prior to Isatuximab 6. Isatuximab 10mg/kg in 250ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of isatuximab administration varies and is dependant the occurrence and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC or PE administration sets must be used. 7. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 8. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 9. Paracetamol 1000mg oral when required for the relief of infusion related reactions Administration Instructions Please check if the patient takes regular paracetamol for pain control and take dose into account 10. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions 11. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Version 2 (February 2024) Page 13 of 18 Myeloma – Isatuximab- Dexamethasone (40)-Pomalidomide Cycle 1 Days 8, 15 and 22 12. Chlorphenamine 10mg intravenous Administration Instructions Administer 15 – 60 minutes prior to Isatuximab 13. Dexamethasone 40mg oral Administration Instructions Administer 15 – 60 minutes prior to Isatuximab Administer 40mg once a day orally. For those unable to tolerate the oral route this can be administered at an equivalent intravenous dose. Reduce dose to 20mg orally or intravenous equivalent if the patient is over 75 years old. 14. Paracetamol 1000mg oral Administration Instructions Administer 15 – 60 minutes prior to Isatuximab Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 15. Omeprazole 20mg Oral Administration Instructions Administer 15 – 60 minutes prior to Isatuximab 16. Isatuximab 10mg/kg in 250ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of isatuximab administration varies and is dependant the occurrence and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC or PE administration sets must be used. 17. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 18. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 19. Paracetamol 1000mg oral when required for the relief of infusion related reactions Administration Instructions Please check if the patient takes regular paracetamol for pain control and take dose into account 20. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions 21. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Take home medicines (day 1 only) 22. Warning – Pregnancy Prevention Programme Administration Instructions Pomalidomide is associated with a pregnancy prevention programme. Please ensure this is completed for all patients. 23. Pomalidomide 4mg once a day on days 1-21 oral Administration Information Oral SACT Pregnancy prevention programme Take at the same time each day. Swallow the capsules whole, preferably with water, with or without food. Version 2 (February 2024) Page 14 of 18 Myeloma – Isatuximab- Dexamethasone (40)-Pomalidomide 24. Allopurinol 300mg once a day for 7 days, oral Administration information Take in the morning with food and plenty of water. This should be supplied for the first cycle only. 25. Aciclovir 400mg twice a day for 28 days oral Administration Instructions Please supply 28 days or an original pack if appropriate. 26. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 28 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 28 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice. 27. Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - esomeprazole 20mg once a day oral - omeprazole 20mg once a day oral - lansoprazole 15mg once a day oral - pantoprazole 20mg once a day oral - rabeprazole 20mg once a day oral - cimetidine 400mg twice a day oral - famotidine 20mg once a day oral - nizatidine 150mg twice a day oral - ranitidine 150mg twice a day oral Please supply 28 days or the nearest original pack size. 28. Thromboprophylaxis according to risk factors Administration Instructions The choice of thromboprophylaxis is dependent on local formularly choice and may include; - dalteparin 5000units once a day subcutaneous injection - enoxaparin 40mg once a day subcutaneous injection - heparin 5000units twice a day subcutaneous injection - apixaban 2.5mg TWICE a day ORAL or equivalent NOAC Please supply 28 days or nearest original pack size. Aspirin may be considered after cycle six of treatment. Cycle 2 Days 1 and 15 29. Chlorphenamine 10mg intravenous Administration Instructions Administer 15 – 60 minutes prior to Isatuximab 30. Dexamethasone 40mg oral Administration Instructions Administer 15 – 60 minutes prior to Isatuximab Administer 40mg once a day orally. For those unable to tolerate the oral route this can be administered at an equivalent intravenous dose. Reduce dose to 20mg orally or intravenous equivalent if the patient is over 75 years old. 31. Paracetamol 1000mg oral Administration Instructions Administer 15 – 60 minutes prior to Isatuximab Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 32. Omeprazole 20mg Oral Administration Instructions Administer 15 – 60 minutes prior to Isatuximab 33. Isatuximab 10mg/kg in 250ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of isatuximab administration varies and is dependant the occurrence and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Version 2 (February 2024) Page 15 of 18 Myeloma – Isatuximab- Dexamethasone (40)-Pomalidomide Polyurethane (PU), polybutadiene (PBD), PVC or PE administration sets must be used. 34. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 35. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 36. Paracetamol 1000mg oral when required for the relief of infusion related reactions Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 37. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions 38. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Take home medicines (day 1 only) 39. Dexamethasone 40mg on days 8 and 22, oral Administration Information Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice. 40. Warning – Pregnancy Prevention Programme Administration Instructions Pomalidomide is associated with a pregnancy prevention programme. Please ensure this is completed for all patients. 41. Pomalidomide 4mg once a day on days 1-21 oral Administration Information Oral SACT Pregnancy prevention programme Take at the same time each day. Swallow the capsules whole, preferably with water, with or without food. 42. Aciclovir 400mg twice a day for 28 days oral Administration Instructions Please supply 28 days or an original pack if appropriate. 43. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 28 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 28 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice. 44. Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - esomeprazole 20mg once a day oral - omeprazole 20mg once a day oral - lansoprazole 15mg once a day oral - pantoprazole 20mg once a day oral - rabeprazole 20mg once a day oral - cimetidine 400mg twice a day oral - famotidine 20mg once a day oral - nizatidine 150mg twice a day oral - ranitidine 150mg twice a day oral Please supply 28 days or the nearest original pack size. Version 2 (February 2024) Page 16 of 18 Myeloma – Isatuximab- Dexamethasone (40)-Pomalidomide 45. Thromboprophylaxis according to risk factors Administration Instructions The choice of thromboprophylaxis is dependent on local formularly choice and may include; - dalteparin 5000units once a day subcutaneous injection - enoxaparin 40mg once a day subcutaneous injection - heparin 5000units twice a day subcutaneous injection - apixaban 2.5mg TWICE a day ORAL or equivalent NOAC Please supply 28 days or nearest original pack size. Aspirin may be considered after cycle six of treatment. . Version 2 (February 2024) Page 17 of 18 Myeloma – Isatuximab- Dexamethasone (40)-Pomalidomide DOCUMENT CONTROL Version Date Amendment Written By Approved By 1 June 2020 None Nanda Basker Pharmacist 2 February 2024 Pre-medication timings and national dose banding for Isatuximab Nanda Basker Pharmacist Dr M Jenner Consultant Haematologist This chemotherapy protocol has been developed as part of the chemotherapy electronic prescribing project. This was and remains a collaborative project that originated from the former CSCCN. These documents have been approved on behalf of the following Trusts; Hampshire Hospitals NHS Foundation Trust NHS Isle of Wight Portsmouth Hospitals NHS Trust Salisbury NHS Foundation Trust University Hospital Southampton NHS Foundation Trust Western Sussex Hospitals NHS Foundation Trust All actions have been taken to ensure these protocols are correct. However, no responsibility can be taken for errors that occur as a result of following these guidelines. Version 2 (February 2024) Page 18 of 18 Myeloma – Isatuximab- Dexamethasone (40)-Pomalidomide
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DVd Weekly Daratumumab-Bortezomib-Dexamethasone Cycles 1 to 8
Description
Chemotherapy Protocol Myeloma DVd (Weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) Regimen • Myeloma – Bortezomib (weekly)-Daratumumab-Dexamethasone Indication • Daratumumab in combination with bortezomib and dexamethasone is recommended for use within the Cancer Drugs Fund as an option for treating relapsed multiple myeloma in people who have had 1 previous treatment. • This weekly bortezomib regimen is for patients who experience neuropathy or those with pre-existing neuropathy. Note both the twice weekly and weekly bortezomib regimens include 32 doses of bortezomib; therefore bortezomib continues to the end of cycle 10 in the weekly regimen. Ensure the correct regimen selected. Toxicity Drug Bortezomib Daratumumab Dexamethasone Adverse Effect GI disturbances, peripheral neuropathy, hypotension, dizziness, blurred vision, headache, musculoskeletal pain, pyrexia Infusion related reactions, hypotension, headache, rash, urticaria, pruritus, nausea, vomiting, respiratory tract infections (including pneumonia), neutropenia, thrombocytopenia, anaemia, lymphopenia, peripheral neuropathy, diarrhoea, muscle spasms, fatigue, pyrexia and peripheral oedema, blood transfusion related events Weight gain, gastrointestinal disturbances, hyperglycaemia, CNS disturbances, Cushingoid changes, glucose intolerance. The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Monitoring Drugs • FBC, U&Es, Ca2+ and LFTs prior to day one of each cycle of treatment. • Paraprotein and / or light chains prior to each cycle. • All patients should be tested for hepatitis B virus (HBV) before initiating treatment with daratumumab. Those patients who test positive for HBV infection should be discussed with a consultant specialising in HBV prior to initiating treatment with daratumumab to plan monitoring requirements whilst on treatment. Patients may also be tested for hepatitis C, CMV and HIV at the same time if clinically appropriate. Version 1(July 2019) Page 1 of 14 Myeloma –DVd (weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) • Send a blood sample to transfusion and inform patient and transfusion laboratory that patient is due to commence daratumumab. Patient will require red cell phenotyping as cross match fails due to binding of daratumumab to red cells. • Regular monitoring of blood glucose is considered good practice due to dexamethasone use. Dose Modifications The dose modifications listed are for haematological, liver and renal function and drug specific toxicities only. Dose adjustments may be necessary for other toxicities as well. In principle all dose reductions due to adverse drug reactions should not be re-escalated in subsequent cycles without consultant approval. It is also a general rule for chemotherapy that if a third dose reduction is necessary treatment should be stopped. Please discuss all dose reductions / delays with the relevant consultant before prescribing, if appropriate. The approach may be different depending on the clinical circumstances. Haematological No dose reductions of daratumumab are recommended. Dose delay may be required to allow recovery of blood cell counts in the event of haematological toxicity. Always refer to the responsible consultant, as any dose delays will be dependent on clinical circumstances and treatment intent. Low counts can be a consequence of bone marrow infiltration as well as drug toxicity. Consider blood transfusion or the use of erythropoietin according to NICE TA323 if patient symptomatic of anaemia or where the haemoglobin is less than 8g/dL (80g/L). Consider growth factor support as an alternative to the options below, particularly where there is evidence of bone marrow suppression. To initiate a new cycle of daratumumab, the neutrophil count should be 1x109/L or greater and the platelet count should be 50x109/L or greater, unless the low counts are due to bone marrow infiltration with myeloma. In this situation the daratumumab may be administered at the discretion of the treating consultant haematologist with the appropriate blood product and growth factor support. Neutrophils (x109/L) Dose Modifications (Daratumumab and Bortezomib) Less than 0.5x109/L or febrile neutropenia (fever greater than or equal to 38.5°C and neutrophils less than 1) Interrupt daratumumab treatment and monitor FBC weekly. Once neutrophils recover to 1x109/L, resume daratumumab at a dose of 16mg/kg. Bortezomib - Consider treatment delay or dose reduction or growth factor support. Seek consultant advice. Platelets (x109/L) Dose Modifications Daratumumab Less than 50x109/L Bortezomib Less than 25x109/L Interrupt daratumumab treatment and monitor FBC weekly. Once platelets recover to 50x109/L or greater resume daratumumab at a dose of 16mg/kg. Consider treatment delay or dose reduction or platelet transfusion. Seek consultant advice. Version 1(July 2019) Page 2 of 14 Myeloma –DVd (weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) Hepatic Impairment Please note that the approach may be different where abnormal liver function tests are due to disease involvement. Drug Bortezomib Daratumumab Bilirubin µmol/L AST/ALT units/L Dose (% of original dose) 1.5xULN or below greater than 1.5xULN N/A 100% Initiate treatment at 0.7mg/m2. The dose may be escalated to N/A 1mg/m2 or reduced to 0.5mg/m2 in subsequent cycles based on patient tolerability. No formal studies of daratumumab in patients with hepatic impairment have been conducted. Based on population pharmacokinetic analysis no dosage adjustments are necessary for patients with hepatic impairment Renal Impairment Drug Bortezomib Creatinine Clearance (ml/min) greater than 20 Dose (% of original dose) 100% 20 and below Clinical decision Daratumumab No adjustments necessary Other Dose reductions or interruptions in therapy are not necessary for those toxicities that are considered unlikely to be serious or life threatening. For example, alopecia, altered taste or nail changes Bortezomib For patients experiencing NCI-CTC grade 1 neuropathy without loss of function or pain continue with full dose bortezomib. For NCI-CTC grade 1 with pain or grade 2 neuropathy reduce the dose of bortezomib to 1mg/m2. For NCI-CTC grade 2 with pain or grade 3 neuropathy discontinue treatment until symptoms have resolved to NCI-CTC grade 1 or less then reinitiate bortezomib at a dose of 0.7mg/m2 For NCI-CTC grade 4 neuropathy and/or severe autonomic neuropathy discontinue bortezomib. For any other NCI-CTC grade 3 non haematological toxicity bortezomib should be discontinued until symptoms have resolve to NCI-CTC grade 1 or below. On the first occurrence treatment may be reinitiated at a dose of 1mg/m2. Following second occurrence to dose should be further reduced to 0.7mg/m2 once symptoms have resolved. Version 1(July 2019) Page 3 of 14 Myeloma –DVd (weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) If the toxicity is not resolved or if it recurs at the lowest dose, discontinuation of bortezomib must be considered unless the benefit of treatment clearly outweighs the risk. Dexamethasone For patients who are elderly or unable to tolerate the standard dose of dexamethasone the dose given the day after bortezomib alone (days 8 and 15 from cycle 4 onwards) may be reduced. Please note the doses before and the day after each daratumumab are to reduce the risk of infusion related reactions and as a steroid component of the triple combination. Infusion related reactions (IRR) Infusion reactions are reported in approximately half of patients who receive daratumumab and may occur up to 48 hours after the infusion has finished. The majority of infusion related reactions, 46%, occur with the first infusion, 2% with the second infusion and 3% with subsequent infusions. Signs and symptoms include bronchospasm, hypoxia, dyspnoea, hypertension, respiratory symptoms such as cough, wheezing, larynx and throat tightness and irritation, laryngeal oedema, pulmonary oedema, nasal congestion and allergic rhinitis. For infusion reactions of any grade/severity, immediately interrupt the infusion and manage the symptoms. Management of infusion reactions may further require reduction in the rate of infusion, or treatment discontinuation as outlined below. IRR grade Grade 1-2 (mild to moderate) Grade 3 (severe) Grade 4 (life threatening) Dose modification Once symptoms resolve, resume the infusion at no more than half the rate at which the reaction occurred. If the patient does not experience any further reaction symptoms, infusion rate escalation may resume at increments and intervals as appropriate. If the intensity of the reaction decreases to ≤Grade 2, consider restarting the infusion at no more than half the rate at which the reaction occurred. If the patient does not experience additional symptoms, resume infusion rate escalation at increments and intervals as appropriate. Permanently discontinue treatment upon the third occurrence of a Grade 3 or greater reaction. Permanently discontinue treatment. Version 1(July 2019) Page 4 of 14 Myeloma –DVd (weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) Regimen 21 day cycle. Continue daratumumab until disease progression. Note that cycle length changes to 28 days from cycle 9 onwards. Cycles 1 to 3 Drug Bortezomib Daratumumab Dose 1.3mg/m2 16mg/kg 20mg once a day Dexamethasone (iv dose equivalent) Dexamethasone 20mg once a day Days 1,8,15 1,8,15 1, 8, 15 2, 9, 16 Administration Subcutaneous Intravenous infusion in 500ml sodium chloride 0.9% IV bolus Can be given as 20mg orally from second infusion onwards. Reduce dose to 10mg orally (or iv dose equivalent) in over 75yrs Oral Reduce dose to 10mg in over 75yrs Cycles 4 to 8 Drug Bortezomib Daratumumab Dose 1.3mg/m2 16mg/kg Dexamethasone 20mg once a day Dexamethasone 20mg once a day Days 1,8,15 1 1 2, 8, 9, 15, 16 Administration Subcutaneous Intravenous infusion in 500ml sodium chloride 0.9% Orally Can be given as 20mg intravenous equivalent. Reduce dose to 10mg orally (or iv dose equivalent) in over 75yrs Oral Reduce dose to 10mg in over 75yrs Cycles 9 onwards – see separate protocol Version 1(July 2019) Page 5 of 14 Myeloma –DVd (weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) Dose Information • Daratumumab will be prescribed in accordance with the national dose bands (20 NS). • Bortezomib dose will be dose banded in accordance with the national dose bands (2.5). • Dexamethasone is available as 2mg and 500microgram tablets and 3.3mg in 1ml injection (equivalent to 4mg orally) Administration Information • The rate of daratumumab administration varies and depends on infusion related reactions. In order to determine the rate of the second and ongoing infusions all reactions and the first reaction free infusion must be recorded in the ARIA journal. • Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an in-line, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC, PP or PE administration sets must be used. First infusion Second infusionb Subsequent infusionsc Final volume 500ml 500ml 500ml Initial rate (first hour) 25ml/hour 50ml/hour 100ml/hour Rate incrementa 25ml/hour every hour 50ml/hour every hour 50ml/hour every hour Maximum rate 100ml/hour 200ml/hour 200ml/hour a Consider the incremental escalation of the infusion rate only in the absence of infusion reactions with the previous infusion b Escalate only if the patient’s first infusion of daratumumab was well tolerated (defined by an absence of NCI-CTC grade 2 or greater infusion-related reactions during the first 3 hours). If the previous infusion was not well tolerated then instructions for the first infusion c Escalate only if the patient’s first 2 infusions of daratumumab were well tolerated (defined by an absence of NCI-CTC grade 1 or greater infusion-related reactions during a final infusion rate of greater than or equal to 100 ml/hr). If the previous infusion was not well tolerated, then instructions for the second infusion will be used. For guidance on infusion rates in the case of infusion related reactions. See the managing infusion reactions section above. Rapid Infusion Protocol Data from a prospective, single-center and open label safety study of an accelerated daratumumab infusion suggests that a rapid (90 minute) daratumumab infusion schedule is well tolerated and safe, when administered from the 3rd infusion onwards in patients who have tolerated the 500mL daratumumab infusion at the manufacturer recommended rates. • The rapid rate of infusion is currently unlicensed. Version 1(July 2019) Page 6 of 14 Myeloma –DVd (weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) Inclusion criteria for daratumumab rapid rate infusion • Patients from third daratumumab infusion onwards who have received and tolerated the previous daratumumab 100mL/hour initial infusion rate with escalation to the standard manufacturer licensed rate without Grade 1 infusion related reactions. • Patients who have given consent to rapid rate daratumumab infusion if required by the individual Trust Exclusion criteria for daratumumab rapid rate infusion • Previous greater than or equal to grade 3 infusion related toxicity with daratumumab • Infusion related reactions greater than or equal to grade 1 with the most recent daratumumab infusion given at the standard manufacturer licensed rate. • Cardiac amyloid patients • Patients receiving daratumumab as part of clinical trials (follow trial protocol) Rapid infusion rate Daratumumab prepared in 500mL sodium chloride 0.9% • Infuse 100mL of the daratumumab infusion (20%) of the dose over 30 minutes • Then infuse the remaining 400mL (80% of the dose) over 60 minutes (total infusion time 90 minutes). Monitoring • Check vital signs before the start of the infusion, every 15 minutes during the first 60 minutes of the infusion and at the end of the infusion for all daratumumab infusions. • Monitor patient for adverse effects. For the first rapid rate infusion, observe patients in the Day Unit for 30 minutes after infusion completion to assess for delayed infusion related reactions. • Closer monitoring is required if the patient has a history of uncontrolled hypertension, pre-existing COPD, asthma or other respiratory comorbidities. These patients should be discussed with the consultant. Additional therapy • Consider allopurinol 300mg once a day for seven days for the first cycle only oral • No anti-emetics are required • Premedication required 1 to 3 hours before every daratumumab infusion: - dexamethasone see regimen for dose details - chlorphenamine 10mg intravenous - paracetamol 1000mg oral - montelukast 10mg oral for the first two cycles only and the first “fast infusion” if this does not occur on cycle two • Consider anti-infective prophylaxis including: - aciclovir 400mg twice a day oral Version 1(July 2019) Page 7 of 14 Myeloma –DVd (weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) - co-trimoxazole 960mg once a day oral on Monday, Wednesday and Friday only - fluconazole 100mg once a day oral if recurrent oral candidiasis • Bisphosphonates in accordance with local policies. • Mouthwashes according to local or national policy on the treatment of mucositis. • Gastric protection with a proton pump inhibitor or an H2 antagonist may be considered in patients considered at high risk of GI ulceration or bleed. • As required for the treatment of infusion related reactions for patients at high risk of respiratory complications: - sodium chloride 0.9% 500ml intravenous - salbutamol 2.5mg nebulised - hydrocortisone sodium succinate 100mg intravenous - chlorphenamine 10mg intravenous - paracetamol 1000mg oral - oxygen as required Additional Information • All instances of infusion related reaction must be recorded on ARIA. Daratumumab will continue to be administered at the cycle one rate until a reaction free infusion is noted. • Daratumumab interferes with indirect antiglobulin tests as it binds to CD38 on red blood corpuscles (RBCs) and interferes with compatibility testing, including antibody screening and cross matching. Daratumumab interference mitigation methods include treating reagent RBCs with dithiothreitol (DTT) to disrupt daratumumab binding or other locally validated methods. Since the Kell blood group system is also sensitive to DTT treatment, Kell-negative units should be supplied after ruling out or identifying alloantibodies using DTT-treated RBCs. Alternatively, phenotyping or genotyping may also be considered. • Daratumumab may be detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for monitoring disease monoclonal immunoglobulins (M protein). This can lead to false positive SPE and IFE assay results for patients with IgG kappa myeloma protein impacting initial assessment of complete responses by International Myeloma Working Group (IMWG) criteria. In patients with persistent very good partial response, consider other methods to evaluate the depth of response. Coding • Procurement –X70.8 • Delivery – X72.9, X72.4 Version 1(July 2019) Page 8 of 14 Myeloma –DVd (weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) References 1. Janssen-Cilag Limited (18 Dec 2018). Darzalex 20mg/ml Summary of Product Characteristics. Electronic Medicines Compendium. Online at https://www.medicines.org.uk/emc/product/7250 , accessed 01 July 2019. 2. National Institute for Health and Care Excellence (2019). Daratumumab with bortezomib and dexamethasone for previously treated multiple myeloma. [TA573]. London: National Institute for Health and Care Excellence. 3. Thames Valley Strategic Cancer Network Myeloma Group MM47 DaraVelDex Protocol version 2.0 April 2019. 4. 90 minute daratumumab infusion is safe in multiple myeloma. Leukemia. Hallie Barr et al. Accessed 27/11/18 https://doi.org/10.1038/s41375-018-0120-2. Version 1(July 2019) Page 9 of 14 Myeloma –DVd (weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) REGIMEN SUMMARY Myeloma – DVd (Weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) Cycles 1 Day 1, 8, 15 1. Warning – Inform blood transfusion Administration Instructions Daratumumab interferes with indirect antiglobulin tests as it binds to CD38 on red blood corpuscles (RBCs) and interferes with compatibility testing, including antibody screening and cross matching. Daratumumab interference mitigation methods include treating reagent RBCs with dithiothreitol (DTT) to disrupt daratumumab binding or other locally validated methods. Since the Kell blood group system is also sensitive to DTT treatment, Kell-negative units should be supplied after ruling out or identifying alloantibodies using DTT-treated RBCs. Alternatively, phenotyping or genotyping may also be considered. Daratumumab may be detected on serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for monitoring disease monoclonal immunoglobulins (M protein). This can lead to false positive SPE and IFE assay results for patients with IgG kappa myeloma protein impacting initial assessment of complete responses by International Myeloma Working Group (IMWG) criteria. In patients with persistent very good partial response, consider other methods to evaluate the depth of response Please inform blood transfusion when a patient is prescribed daratumumab 2. Chlorphenamine 10mg intravenous 3. Dexamethasone 20mg intravenous equivalent Administration Instructions Administer 20mg intravenous equivalent – Can be administered as 20mg orally from second infusion onwards. Reduce dose to 10mg intravenous equivalent or 10mg orally in patients over 75 years old. 4. Paracetamol 1000mg oral Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 5. Montelukast 10mg oral 6. Daratumumab 16mg/kg in 500ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of daratumumab administration varies and is dependant the occurance and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC, PP or PE administration sets must be used. 7. Bortezomib 1.3mg/m2 subcutaneous injection 8. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 9. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 10. Paracetamol 1000mg oral when required for the relief of infusion related reactions 11. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions 12. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Version 1(July 2019) Page 10 of 14 Myeloma –DVd (weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) Cycles 1 Take home medicines (day 1 only) 13. Dexamethasone 20mg on days 2, 9 and 16 oral Administration Information Reduce dose to 10mg in patients over 75 years old Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice. 14. Allopurinol 300mg once a day for 7 days oral Administration information Take in the morning with food and plenty of water. This should be supplied for the first cycle only. 15. Aciclovir 400mg twice a day for 21 days oral Administration Instructions Please supply 21 days or an original pack if appropriate. 16. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 21 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 21 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice. 17. Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - esomeprazole 20mg once a day oral - omeprazole 20mg once a day oral - lansoprazole 15mg once a day oral - pantoprazole 20mg once a day oral - rabeprazole 20mg once a day oral - cimetidine 400mg twice a day oral - famotidine 20mg once a day oral - nizatidine 150mg twice a day oral - ranitidine 150mg twice a day oral Please supply 21 days or the nearest original pack size. Cycles 2 and 3 days 1, 8, 15 18. Chlorphenamine 10mg intravenous 19. Dexamethasone 20mg orally Administration Instructions Administer 20mg orally. Can be administered as 20mg intravenous equivalent. Reduce dose to 10mg intravenous equivalent or 10mg orally in patients over 75 years old.. 20. Paracetamol 1000mg oral Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours 21. Montelukast 10mg oral Administration Instructions Administer during the first two cycles (six infusions). Also administer before the first ‘fast infusion’ if this occurs after cycle 2. 22. Daratumumab 16mg/kg in 500ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of daratumumab administration varies and is dependant the occurance and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC, PP or PE administration sets must be used. 23. Bortezomib 1.3mg/m2 subcutaneous injection Version 1(July 2019) Page 11 of 14 Myeloma –DVd (weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) 24. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 25. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 26. Paracetamol 1000mg oral when required for the relief of infusion related reactions 27. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions 28. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Cycles 2 and 3 Take home medicines (day 1 only) 29. Dexamethasone 20mg on days 2, 9 and 16 oral Administration Information Reduce dose to 10mg in patients over 75 years old Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice. 30. Aciclovir 400mg twice a day for 21 days oral Administration Instructions Please supply 21 days or an original pack if appropriate. 31. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 21 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 21 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice. 32. Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - esomeprazole 20mg once a day oral - omeprazole 20mg once a day oral - lansoprazole 15mg once a day oral - pantoprazole 20mg once a day oral - rabeprazole 20mg once a day oral - cimetidine 400mg twice a day oral - famotidine 20mg once a day oral - nizatidine 150mg twice a day oral - ranitidine 150mg twice a day oral Please supply 21 days or the nearest original pack size. Cycles 4 to 8 day 1 33. Chlorphenamine 10mg intravenous 34. Dexamethasone 20mg orally Administration Instructions Administer 20mg orally. Can be administered as 20mg intravenous equivalent. Reduce dose to 10mg intravenous equivalent or 10mg orally in patients over 75 years old.. 35. Paracetamol 1000mg oral Administration Instructions Please check if the patient has taken paracetamol. The maximum dose is 4000mg/24 hours Version 1(July 2019) Page 12 of 14 Myeloma –DVd (weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) 36. Daratumumab 16mg/kg in 500ml sodium chloride 0.9% intravenous infusion Administration Instructions The rate of daratumumab administration varies and is dependant the occurance and severity of infusion related reactions. Please refer to the protocol for details of the rate of administration and management of such reactions Administer the diluted solution by intravenous infusion using an infusion set fitted with a flow regulator and with an inline, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.22 or 0.2 micrometre). Polyurethane (PU), polybutadiene (PBD), PVC, PP or PE administration sets must be used. 37. Bortezomib 1.3mg/m2 subcutaneous injection 38. Chlorphenamine 10mg intravenous when required for the relief of infusion related reactions 39. Hydrocortisone 100mg intravenous when required for the relief of infusion related reactions 40. Paracetamol 1000mg oral when required for the relief of infusion related reactions 41. Salbutamol 2.5mg nebulised when required for the relief of infusion related reactions 42. Sodium chloride 0.9% 500ml intravenous infusion when required for the relief of infusion related reactions Cycles 4 to 8 days 8 and 15 43. Bortezomib 1.3mg/m2 subcutaneous injection Cycles 4 to 8 Take home medicines (day 1 only) 44. Dexamethasone 20mg on days 2, 8, 9, 15 and 16 oral Administration Information Reduce dose to 10mg in patients over 75 years old Take in the morning with or after food. Please dispense all days on day 1 of the cycle. This may be dispensed in one bottle, or individual bottles according to local practice. 45. Aciclovir 400mg twice a day for 21 days oral Administration Instructions Please supply 21 days or an original pack if appropriate. 46. Co-trimoxazole 960mg once a day on Monday, Wednesday and Friday only for 21 days oral Administration Instructions Co-trimoxazole 960mg once a day on Mondays, Wednesdays and Fridays. Please supply 21 days. This may be dispensed as 480mg twice a day on Mondays, Wednesdays and Fridays according to local practice. 47. Gastric Protection Administration Instructions The choice of gastric protection is dependent on local formulary choice and may include; - esomeprazole 20mg once a day oral - omeprazole 20mg once a day oral - lansoprazole 15mg once a day oral - pantoprazole 20mg once a day oral - rabeprazole 20mg once a day oral - cimetidine 400mg twice a day oral - famotidine 20mg once a day oral - nizatidine 150mg twice a day oral - ranitidine 150mg twice a day oral Please supply 21 days or the nearest original pack size. Version 1(July 2019) Page 13 of 14 Myeloma –DVd (weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8) DOCUMENT CONTROL Version Date Amendment Written By Approved By 1 July 2019 None Harriet Launders Pharmacist Dr Deborah Wright Pharmacist Dr Mathew Jenner Consultant Haematologist This chemotherapy protocol has been developed as part of the chemotherapy electronic prescribing project. This was and remains a collaborative project that originated from the former CSCCN. These documents have been approved on behalf of the following Trusts; Hampshire Hospitals NHS Foundation Trust NHS Isle of Wight Portsmouth Hospitals NHS Trust Salisbury NHS Foundation Trust University Hospital Southampton NHS Foundation Trust Western Sussex Hospitals NHS Foundation Trust All actions have been taken to ensure these protocols are correct. However, no responsibility can be taken for errors that occur as a result of following these guidelines. These protocols should be used in conjunction with other references such as the Summary of Product Characteristics and relevant published papers. Version 1(July 2019) Page 14 of 14 Myeloma –DVd (weekly) Bortezomib-Daratumumab-Dexamethasone (cycles 1 to 8)
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Papers Trust Board - 13 January 2026
Description
Date Time Location Chair Apologies Agenda Trust Board – Open Session 13/01/2026 9:00 - 13:00 Conference Room, Heartbeat Education Centre Jenni Douglas-Todd Diana Eccles 1 Chair’s Welcome, Apologies and Declarations of Interest 9:00 Note apologies for absence, and to hear any declarations of interest relating to any item on the Agenda. 2 Patient Story The patient story provides an opportunity for the Board to reflect on the experiences of patients and staff within the Trust and understand what the Trust could do better. 3 Minutes of Previous Meeting held on 11 November 2025 9:15 Approve the minutes of the previous meeting held on 11 November 2025 4 Matters Arising and Summary of Agreed Actions To discuss any matters arising from the minutes, and to agree on the status of any actions assigned at the previous meeting. 5 QUALITY, PERFORMANCE and FINANCE Quality includes: clinical effectiveness, patient safety, and patient experience 5.1 Briefing from the Chair of the Finance, Investment & Cash Committee 9:20 David Liverseidge, Chair 5.2 Briefing from the Chair of the People and Organisational Development 9:30 Committee Jane Harwood, Chair 5.3 Briefing from the Chair of the Quality Committee 9:40 including Maternity and Neonatal Safety 2025-26 Quarter 2 Report Tim Peachey, Chair 5.4 Chief Executive Officer's Report 9:50 Receive and note the report Sponsor: David French, Chief Executive Officer 5.5 Performance KPI Report for Month 8 10:20 Review and discuss the report Sponsor: Andy Hyett, Chief Operating Officer 5.6 11:00 5.7 11:15 5.8 11:25 5.9 11:30 5.10 11:45 5.11 11:55 5.12 12:05 5.13 12:15 6 6.1 12:25 7 12:35 8 Break Finance Report for Month 8 Review and discuss the report Sponsor: Ian Howard, Chief Financial Officer ICB System Report for Month 8 Receive and discuss the report Sponsor: Ian Howard, Chief Financial Officer People Report for Month 8 Review and discuss the report Sponsor: Steve Harris, Chief People Officer Learning from Deaths 2025-26 Quarter 2 Report Review and discuss the report Sponsor: Paul Grundy, Chief Medical Officer Attendee: Jenny Milner, Associate Director of Patient Experience Infection Prevention and Control 2025-26 Quarter 2 Report Review and discuss the report Sponsor: Natasha Watts, Acting Chief Nursing Officer Attendees: Julian Sutton, Clinical Lead, Department of Infection/Julie Brooks, Deputy Director of Infection Prevention and Control Medicines Management Annual Report 2024-25 Receive and discuss the report Sponsor: Paul Grundy, Chief Medical Officer Attendee: James Allen, Chief Pharmacist Annual Ward Staffing Nursing Establishment Review 2025 Discuss and approve the review Sponsor: Natasha Watts, Acting Chief Nursing Officer CORPORATE GOVERNANCE, RISK and INTERNAL CONTROL Annual Assurance for the NHS England Core Standards for Emergency Preparedness, Resilience and Response (EPRR) Review and discuss the report Sponsor: Andy Hyett, Chief Operating Officer Attendee: John Mcgonigle, Emergency Planning & Resilience Manager Any other business Raise any relevant or urgent matters that are not on the agenda Note the date of the next meeting: 10 March 2026 Page 2 9 Resolution regarding the Press, Public and Others Sponsor: Jenni Douglas-Todd, Trust Chair To agree, as permitted by the National Health Service Act 2006 (as amended), the Trust's Constitution and the Standing Orders of the Board of Directors, that representatives of the press, members of the public and others not invited to attend to the next part of the meeting be excluded due to the confidential nature of the business to be transacted. 10 Follow-up discussion with governors 12:45 Page 3 Agenda links to the Board Assurance Framework (BAF) 13 January 2026 – Open Session Overview of the BAF Risk 1a: Lack of capacity to appropriately respond to emergency demand, manage the increasing waiting lists for elective demand, and provide timely diagnostics, that results in avoidable harm to patients. 1b: Due to the current challenges, we fail to provide patients and their families / carers with a high-quality experience of care and positive patient outcomes. 1c: We do not effectively plan for and implement infection prevention and control measures that reduce the number of hospital-acquired infections and limit the number of nosocomial outbreaks of infection. 2a: We do not take full advantage of our position as a leading University teaching hospital with a growing, reputable, and innovative research and development portfolio, attracting the best staff and efficiently delivering the best possible treatments and care for our patients. 3a: We are unable to meet current and planned service requirements due to the unavailability of staff to fulfil key roles. 3b: We fail to develop a diverse, compassionate, and inclusive workforce, providing a more positive staff experience for all staff. 3c: We fail to create a sustainable and innovative education and development response to meet the current and future workforce needs identified in the Trust’s longer-term workforce plan. 4a: We do not implement effective models to deliver integrated and networked care, resulting in sub-optimal patient experience and outcomes, increased numbers of admissions and increases in patients’ length of stay. 5a: We are unable to deliver a financial breakeven position, resulting in: inability to move out of the NHS England Recovery Support Programme, NHS England imposing additional controls/undertakings, and a reducing cash balance impacting the Trust’s ability to invest in line with its capital plan, estates/digital strategies, and in transformation initiatives. 5b: We do not adequately maintain, improve and develop our estate to deliver our clinical services and increase capacity. 5c: Our digital technology or infrastructure fails to the extent that it impacts our ability to deliver care effectively and safely within the organisation, 5d: We fail to prioritise green initiatives to deliver a trajectory that will reduce our direct and indirect carbon footprint by 80% by 2028-2032 (compared with a 1990 baseline) and reach net zero direct carbon emissions by 2040 and net zero indirect carbon emissions by 2045. Agenda links to the BAF No Item Linked BAF risk(s) 5.5 Performance KPI Report for Month 8 5.7 Finance Report for Month 8 5.8 ICB System Report for Month 8 5.9 People Report for Month 8 5.10 Learning from Deaths 2025-26 Quarter 2 Report 5.11 Infection Prevention and Control 2025-26 Quarter 2 Report 5.12 Medicines Management Annual Report 2024-25 5.13 Annual Ward Staffing Nursing Establishment Review 2025 6.1 Annual Assurance for the NHS England Core Standards for Emergency Preparedness, Resilience and Response (EPRR) 1a, 1b, 1c 5a 5a 3a, 3b, 3c 1b 1c 1b 1b, 3a 1b Appetite (Category) Minimal (Safety) Current risk rating 4x5 20 Cautious (Experience) Minimal (Safety) 4x4 16 4x4 16 Open (Technology & Innovation) 3x4 12 Open (workforce) Open (workforce) Open (workforce) 4x5 20 4x3 12 4x4 16 Cautious (Effectiveness) 3x3 9 Cautious (Finance) 5x5 25 Target risk rating 4 x 2 Apr 6 27 3 x 2 Apr 6 27 2 x 3 Apr 6 27 3 x 2 Mar 6 27 4 x 3 Mar 12 30 4 x 2 Mar 8 30 3 x 2 Mar 6 29 3 x 2 Dec 6 25 3 x 3 Apr 9 30 Cautious (Effectiveness) Open (Technology & Innovation) Open (Technology & Innovation) 4x5 20 3x4 12 2x4 8 4 x 2 Apr 8 30 3 x 2 Apr 6 27 2 x 2 Dec 4 27 Does this item facilitate movement towards or away from the intended target risk score and appetite? Towards Away Neither x x x x x x x x x Minutes Trust Board – Open Session Date 11/11/2025 Time 9:00 – 13:00 Location Conference Room, Heartbeat Education Centre Chair Jenni Douglas-Todd (JD-T) Present Diana Eccles, NED (DE) Keith Evans, Deputy Chair and NED (KE) David French, Chief Executive Officer (DAF) Paul Grundy, Chief Medical Officer (PG) Steve Harris, Chief People Officer (SH) Jane Harwood, NED/Senior Independent Director (JH) Ian Howard, Chief Financial Officer (IH) Andy Hyett, Chief Operating Officer (AH) David Liverseidge, NED (DL) Tim Peachey, NED (TP) Alison Tattersall, NED (AT) Natasha Watts, Acting Chief Nursing Officer (NW) In attendance Craig Machell, Associate Director of Corporate Affairs and Company Secretary (CM) Lauren Anderson, Corporate Governance and Risk Manager (LA) (item 6.2) Martin de Sousa, Director of Strategy and Partnerships (MdS) (item 6.1) Lucinda Hood, Head of Medical Directorate (LH) (item 5.13) Diana Hulbert, Guardian of Safe Working Hours and Emergency Department Consultant (DH) (item 5.12) Vickie Purdie, Head of Patient Safety (VP) (item 7.3) Kate Pryde, Clinical Director for Improvement and Clinical Effectiveness (KP) (item 5.13) Scott Spencer, Health and Safety Advisor (SS) (item 7.3) 4 governors (observing) 2 members of staff (observing) 1. Chair’s Welcome, Apologies and Declarations of Interest The Chair welcomed attendees to the meeting. There were no interests to declare in the business to be transacted at the meeting. It was noted that no apologies had been received. The Chair provided an overview of meetings she had held and events that she had attended since the previous Board meeting. 2. Patient Story Item deferred to the next meeting. 3. Minutes of the Previous Meeting held on 9 September 2025 The draft minutes tabled to the meeting were agreed to be an accurate record of the meeting held on 9 September 2025, subject to a minor correction at 5.10. Page 1 4. Matters Arising and Summary of Agreed Actions The matters arising and actions were noted. • Actions 1281, 1283 and 1284 were closed. • Action 1282 was to be addressed through item 5.6 below. • In respect of action 1285, the Quality Committee would monitor progress on complaints response times. 5. QUALITY, PERFORMANCE and FINANCE 5.1 Briefing from the Chair of the Audit and Risk Committee Keith Evans was invited to present the Committee Chair’s Report in respect of the meeting held on 13 October 2025, the content of which was noted. It was further noted that: • In terms of the internal audit reports, which had been received by the committee, whilst there were a number of points for the Trust to address, no areas of significant concern had been identified. • There was a focus on ‘imposter fraud’ whereby individuals who had turned up to carry out a shift were not who they claimed to be. Whilst there had been no reported incidents at the Trust, the Trust had implemented controls at the ward level, which would be subject to testing during 2025/26. 5.2 Briefing from the Chair of the Finance, Investment & Cash Committee David Liverseidge was invited to present the Committee Chair’s Reports in respect of the meetings held on 22 September and 3 November 2025, the contents of which were noted. It was further noted that: • In September 2025, the Trust had reported that it was in line with its Financial Recovery Plan. Of the £110m Cost Improvement Programme (CIP) target, 76% had been fully developed. • The committee had reviewed the Finance Report for Month 6 (item 5.8), noting that the Trust had reported an in-month deficit of £5.4m, which was in line with the Financial Recovery Plan. • The committee had expressed concern that 17% of the CIP target was not fully developed and that the Trust was £2.5m off-track in terms of delivery of the target at Month 6. • Whilst progress had been made in terms of addressing patients with no criteria to reside and mental health patients, this remained an area of concern. • The committee considered the NHS England Medium Term Planning Framework, noting that the first submission by the Trust was due prior to Christmas 2025. 5.3 Briefing from the Chair of the People and Organisational Development Committee Jane Harwood was invited to present the Committee Chair’s Reports in respect of the meetings held on 22 September and 3 November 2025, the contents of which were noted. It was further noted that: • There continued to be little improvement in terms of the number of patients with no criteria to reside or mental health patients, which impacted staffing numbers. • The Trust was adopting a harder line in respect of its approach to violence and aggression, which included a greater willingness to exclude individuals. • The current participation rate in the Staff Survey was lower than the national average, which was likely indicative of staff morale and engagement. Page 2 • The Trust’s workforce numbers remained above plan, with limited options available to address this issue, especially in the absence of funding for restructuring costs. 5.4 Briefing from the Chair of the Quality Committee Tim Peachey was invited to present the Committee Chair’s Report in respect of the meeting held on 13 October 2025, the content of which was noted. It was further noted that: • The committee received an update in respect of mental health patients, noting that although there were significant issues in the Emergency Department, the whole pathway for these patients remained a problem. • The committee carried out a six-monthly review of the Trust’s progress against its Quality Priorities, noting that good progress had been made on four of the six priorities and two were slightly behind. 5.5 Chief Executive Officer’s Report David French was invited to present the Chief Executive Officer’s Report, the content of which was noted. It was further noted that: • NHS England had published the Medium Term Planning Framework, which was intended to encourage organisations to think beyond a 12-month time horizon and to progress the NHS 10-Year Plan. The Trust was expected to provide its first submission prior to Christmas 2025, but the detailed planning assumptions had yet to be received from NHS England. It was noted that a more detailed report on the Medium Term Planning Framework was to be received as part of the closed session of the meeting. • The Strategic Commissioning Framework had been published by NHS England, which provided welcome clarifications about the future role of integrated care boards. • The Trust had been placed into Tier 1 for both Urgent and Emergency Care and for Elective performance. There was a national expectation that trusts would have no patients waiting over 65 weeks for elective care by 21 December 2025. Where organisations had more than 100 such patients at the end of October 2025, they had been placed into Tier 1. The Trust was taking steps, including mutual aid, to attempt to address the number of long waiters, but there was insufficient capacity in the system. • Resident doctors were due to strike for a further five-day period commencing on 14 November 2025, having rejected the Government’s latest offer to resolve the ongoing dispute with the British Medical Association. • The Hampshire and Isle of Wight Integrated Care Board and NHS England South East Region had carried out a visit to the Trust’s paediatric hearing services in May 2025. The report, received in October 2025, had been positive about the service. • The Trust and the University of Southampton had been awarded £16.3m by the National Institute for Health and Care Research. The Trust was one of only four organisations out of 15 applications to receive an award. • The NHS Business Services Authority had announced the award of a £1.2bn contract to Infosys to deliver a new and enhanced workforce management system for the NHS to replace the existing Electronic Staff Record system. The 2030 target date for implementation was considered ambitious. Further details would be considered by the People and Organisational Development Committee when available. Page 3 5.6 Performance KPI Report for Month 6 Andy Hyett was invited to present the ‘spotlight’ report in respect of Diagnostics, the content of which was noted. It was further noted that: • Diagnostics performance was a key element of the pathway, as delays in diagnosis had a consequential impact on the overall length of pathways such as those for cancer and patients on a Referral To Treatment pathway. • Although there were some concerns with Diagnostics in the Trust, the Trust, generally, performed better than other organisations. The Board discussed the matters raised in the Diagnostics ‘spotlight’. This discussion is summarised below: • There had been a long-standing issue with waiting times for cystoscopy due to insufficient capacity. However, a plan was being developed to improve the situation, although it was considered appropriate that the plan should also address broader issues with urology as a whole. • There was concern regarding the availability of magnetic resonance imaging (MRI) scanners, particularly as two scanners were out-of-action. It was noted that the current set-up in terms of MRI scanners was not fit for the longer term and a strategy for the future needed to be developed. • There was a disparity between capacity and demand in respect of the neurophysiology service, as this service had previously relied on outsourcing. • Generally, activity was increasing, but overall performance appeared to be declining. There was also the additional financial challenge that Diagnostics was funded under a ‘block’ contract arrangement which did not fully take into account the demand for these services. • There were concerns about the electrical supply capacity at the Southampton General Hospital site and the ability of the Trust to expand its Diagnostic capacity with this limitation. It was considered that a better longer-term model would be for scanners at local community diagnostics centres. Actions Andy Hyett agreed to work on and present at either a future Board meeting or Trust Board Study Session the Trust’s longer-term strategy with respect to MRI scanners and imaging. Andy Hyett agreed to develop a longer-term plan for cystoscopy/urology and to report back to the Board during Quarter 4. Andy Hyett agreed to develop a long-term solution to the neurophysiology service. Andy Hyett was invited to present the Performance KPI Report for Month 6, the content of which was noted. It was further noted that: • The Trust’s Emergency Department had recorded performance of 67.6% against the four-hour standard during September 2025. The department remained busy with c.450 patients and 120 ambulance attendances per day. • There had been some initial performance impacts with the roll out of the MIYA system in the Emergency Department, but this appeared to have now been addressed with performance up to previous levels. • A number of initiatives were being introduced into the Emergency Department in order to improve performance. These included the layout of the service, pathway re-designs, having General Practitioners in the department, and arranging with non-urgent patients to attend at a scheduled time rather than waiting in the department. Page 4 • In October 2025, the Trust had recorded 363 patients waiting over 65 weeks on a Referral To Treatment pathway against a national target of no such patients by the end of December 2025. • The Trust was making use of the independent sector, weekend working, and was requesting capacity from other providers to address the number of patients waiting over 65 weeks. • The planned industrial action by resident doctors posed a challenge, noting that the national expectation was that trusts maintain 95% of their capacity during this period. It was noted that, in contrast to previous instances of industrial action, resident doctors were apparently less forthcoming in terms of whether they intended to participate in the industrial action. • The Trust continued to report one of the lowest Hospital Standardised Mortality Rates in England. • The Trust’s cancer performance, based on a BBC article, was 21 out of 121 trusts. It was noted that whilst the number of patients being referred on a cancer pathway had increased significantly, the number of patients diagnosed with cancer had not materially changed. • There appeared to have been an increase in the number of pressure ulcers and ‘red flag’ incidents. Work was ongoing to address the findings of the pressure ulcer audit which had been presented to the Quality Committee on 2 June 2025. • The number of patients having no criteria to reside and mental health patients remained high. Actions Andy Hyett agreed to clarify the basis of the calculation of the ‘Watch & Reserve antibiotics usage per 1,000 adms’ metric. 5.7 Break 5.8 Finance Report for Month 6 Ian Howard was invited to present the Finance Report for Month 6, the content of which was noted. It was further noted that: • The Trust had submitted its Financial Recovery Plan to NHS England in August 2025, which committed to an additional £23m improvement in the Trust’s financial position to deliver a full-year position of a £54.9m deficit. In the absence of these additional improvements, the Trust had been forecasting a year-end position of a £78m deficit. The revised target was subject to a number of assumptions, including the need for demand management and improvements in non-criteria to reside and mental health patient numbers. • There were a number of risks to the achievement of the Financial Recovery Plan, including whether there would be improvements in mental health and non-criteria to reside and/or steps taken to manage demand, high levels of activity, and whether it would be possible to reduce the workforce and close theatres. The need for the Trust to focus on achieving the 65-week wait target in particular could impact the Trust’s ability to close capacity. • The Trust had reported an in-month deficit of £5.4m (£30.8m year-to-date), which was in line with the trajectory set out in the Financial Recovery Plan. The Trust’s underlying deficit had seen some marginal improvement during the period. • The Trust’s cash position remains an area of significant concern. Cash requests had been made to NHS England, but the latest request for November 2025 had been rejected. It was therefore likely that the Trust would need to manage its supplier payments in accordance with its available cash. Page 5 5.9 ICS System Report for Month 6 Ian Howard was invited to present the ICS System Report for Month 6, the content of which was noted. It was further noted that: • The Hampshire and Isle of Wight Integrated Care System had reported a year- to-date deficit of £48m. • A significant improvement in the run-rate would be required for the system to be able to deliver its 2025/26 plan. • The system was one of the worst in England in terms of the number of beds occupied by patients having no criteria to reside with approximately 23% of beds being occupied by such patients compared with a national average of 12%. • The system was also below plan in terms of its targets for access to General Practitioners and targets relating to mental health patients. It was noted that the performance in these areas had a consequential impact on the Trust’s performance in areas such as urgent and emergency care performance. 5.10 People Report for Month 6 Steve Harris was invited to present the People Report for Month 6, the content of which was noted. It was further noted that: • The overall workforce fell by 73 whole-time-equivalents (WTE) during September 2025 and was reported as being 54 WTE above the Trust’s 2025/26 plan. The reduction in workforce had been driven through a combination of the impact of the recruitment controls, mutually agreed resignation scheme (MARS) leavers, and a significant drop in use of temporary staff during the month. • On 15 October 2025, the Trust had heard the collective grievance brought by the Royal College of Nursing in respect of the removal of enhanced NHS Professionals rates. It was decided not to reverse the decision in order to maintain equity with the rest of the workforce and consistency across other local providers. A number of actions had been agreed following the hearing. • Sickness rates had increased to 3.8%, although the Trust still benchmarked well against peers. • There were concerns about the potential impact of influenza during the winter period and therefore the Trust was taking a number of actions to promote vaccination of staff. The Trust was currently third in terms of uptake in the Region. • The level of participation in the national Staff Survey remained a challenge with only 32% of staff having completed the survey compared with a national average of 38%. It was considered likely that the recent difficult decisions taken and the impact on staff was impacting staff experience and engagement. • The People and Organisational Development Committee would be examining statutory and mandatory training levels together with the latest proposed national changes. Page 6 5.11 NHSE Audit and review of 'Developing Workforce Safeguards' including UHS Self-Assessment Return Natasha Watts was invited to present the NHS England audit and review of ‘Developing Workforce Safeguards’ (2018), including the Trust’s Self-Assessment Return, the content of which was noted. It was further noted that: • ‘Developing Workforce Safeguards’ was published in October 2018 and included a range of standards to assure safe staffing across the workforce. NHS England had initiated an audit, review and improvement plan amidst concern about a national reduction in compliance. • The Trust had submitted a self-assessment as part of this NHS England review. This assessment showed that the Trust continued to comply with the majority of the standards. • The audit exercise has been used as an opportunity to identify opportunities for improvement. Twelve recommendations have been developed, of which nine were assessed as ‘green’ and three as ‘amber’. 5.12 Guardian of Safe Working Hours Quarterly Report and Update on 10-Point Plan Diana Hulbert was invited to present the Guardian of Safe Working Hours Quarterly Report and Update on the 10-Point Plan, the content of which was noted. It was further noted that: • Resident doctors were due to strike for five days from 14 November 2025. This would be the thirteenth strike in recent years. It was noted that, in addition to pay, the dispute also concerned working conditions and the shortage of posts and consequent risk to resident doctors of unemployment. • The Trust had performed a self-assessment against the 10-Point Plan and it was noted that the majority of the plan’s contents had been considered by the Trust for some time. There were also a number of dependencies on the part of NHS England in areas such as lead employer models. • A national review of statutory and mandatory training was expected to enable portability of training records to facilitate staff moving between NHS organisations. • There had been significant improvements in respect of gaps in rotas. 5.13 Annual Clinical Outcomes Summary Luci Hood and Kate Pryde were invited to present the Annual Clinical Outcomes Summary Report, the content of which was noted. It was further noted that: • The paper provided an overview of the clinical outcomes reviewed by the Clinical Assurance Meeting for Effectiveness and Outcomes (CAMEO) over the 12-month period to September 2025. • The majority of specialities provide reports to CAMEO, although outcome data can be more difficult in some areas to capture than in others. • The outcomes reviewed by the CAMEO and outputs from this body were also influencing the development of the Trust’s clinical strategy. • The strains on the capacity of services posed a risk to clinical outcomes. Page 7 • There was potential that a ‘quality’ override could form part of the NHS Oversight Framework in the future, operating in a similar manner to the ‘financial’ override by limiting the segmentations available to an organisation. 6. STRATEGY and BUSINESS PLANNING 6.1 Corporate Objectives 2025-26 Quarter 2 Review Martin De Sousa was invited to present the review of Corporate Objectives 2025/26 for the second quarter, the content of which was noted. It was further noted that: • Of the 12 objectives agreed for 2025/26, six were rated ‘green’, four were ‘amber’ and two were ‘red’. • The ‘red’ rated risks were that relating to the Trust’s financial performance and that relating to the Trust’s achievement of its workforce plan for 2025/26. 6.2 Board Assurance Framework (BAF) Update Lauren Anderson was invited to present the Board Assurance Framework update, the content of which was noted. It was further noted that: • BDO had completed its audit of the Trust’s risk maturity and had presented its report to the Audit and Risk Committee on 13 October 2025. The audit had highlighted a number of strengths including the Board Assurance Framework, risk definition, and use of risk in decision-making. In terms of opportunities for improvement, the audit report suggested some improvements in articulation of operational risks and use of ‘SMART’ methodology for actions. • The Board Assurance Framework had been reviewed by relevant executive directors and committees since it was last presented to the Board. There had been no changes to the ratings or target dates. 7. CORPORATE GOVERNANCE, RISK and INTERNAL CONTROL 7.1 Feedback from the Council of Governors’ (COG) Meeting 28 October 2025 The Chair presented a summary of the Council of Governors’ meeting held on 28 October 2025. It was noted that the meeting had considered the following matters: • Chief Executive Officer’s Performance Report • Governor attendance at Council of Governors’ meetings • Review of the Council of Governors’ Expenses Reimbursement Protocol • Appointment of Jane Harwood as Deputy Chair with effect from 1 October 2025 • Membership engagement • Feedback from the Governors’ Nomination Committee It was noted that the Trust’s work on violence and aggression received particular attention from the Governors. 7.2 Register of Seals and Chair’s Action Report The paper ‘Register of Seals and Chair’s Actions Report’ was presented to the meeting, the content of which was noted. Page 8 It was further noted that one further item had been sealed on 7 November: Deed of Guarantee between University Hospital Southampton NHS Foundation Trust (Guarantor) and CHG-Meridian UK Limited (Beneficiary) regarding the payment and due performance obligations of UHS Estates Limited (UEL) under the Guaranteed Contract and specifically the Stryker Power Tools delivered to UEL under the pre-contract open build period with CHG. Seal number 307 on 7 November 2025. Decision: The Board agreed to ratify the application of the Trust Seal to the documents listed in the ‘Register of Seals and Chair’s Actions Report’ and to the additional document referred to above. 7.3 Health and Safety Services Annual Report 2024-25 Spencer Scott was invited to present the Health and Safety Services Annual Report 2024/25, the content of which was noted. It was further noted that: • The number of incidents reportable pursuant to the Reporting of Injuries, Diseases and Dangerous Occurrences Regulations (RIDDOR) had increased substantially to 68 such incidents compared to 39 in 2023/24. The majority of these incidents related to moving and handling or exposure to infectious diseases. • There was a concern that there had been a reduction in the number of health and safety related reports and escalations whilst at the same time the number of RIDDORs had increased. • Four areas of concern were highlighted: Entonox surveillance of maternity staff, display screen equipment compliance, the Southampton General Hospital loading bay, and workplace temperatures during the summer. 8. Any other business There was no other business. 9. Note the date of the next meeting: 13 January 2026 10. Items circulated to the Board for reading The item circulated to the Board for reading was noted. There being no further business, the meeting concluded. 11. Resolution regarding the Press, Public and Others Decision: The Board resolved that, as permitted by the National Health Service Act 2006 (as amended), the Trust’s Constitution and the Standing Orders of the board of directors, that representatives of the press, members of the public and others not invited to attend to the next part of the meeting be excluded due to the confidential nature of the business to be transacted. The meeting was adjourned. Page 9 List of action items Agenda item Assigned to Deadline Status Trust Board – Open Session 15/07/2025 - 5.11 Freedom to Speak Up Report 1267. Data Mbabazi, Christine 10/03/2026 Pending Explanation action item Christine Mbabazi to include data from other mechanisms for reporting concerns in future Freedom to Speak Up reports. Trust Board – Open Session 09/09/2025 - 8 Any other business 1286. Organ donation Machell, Craig 03/02/2026 Pending Explanation action item Craig Machell agreed to add organ donation to the agenda of a future Trust Board Study Session. Update: Scheduled for TBSS on 03/02/26. Trust Board – Open Session 11/11/2025 - 5.6 Performance KPI Report for Month 6 1293. MRI scanners and imaging Hyett, Andy 13/01/2026 Pending Explanation action item Andy Hyett agreed to work on and present at either a future Board meeting or Trust Board Study Session the Trust’s longer-term strategy with respect to MRI scanners and imaging. 1294. Cystopscopy/urology Hyett, Andy 13/01/2026 Pending Explanation action item Andy Hyett agreed to develop a longer-term plan for cystoscopy/urology and to report back to the Board during Quarter 4. Page 1 of 2 Agenda item Assigned to Deadline Status Trust Board – Open Session 11/11/2025 - 5.6 Performance KPI Report for Month 6 1295. Neurophysiology Hyett, Andy 13/01/2026 Pending Explanation action item Andy Hyett agreed to develop a long-term solution to the neurophysiology service. 1296. Watch & Reserve antibiotics usage Hyett, Andy 13/01/2026 Pending Explanation action item Andy Hyett agreed to clarify the basis of the calculation of the ‘Watch & Reserve antibiotics usage per 1,000 adms’ metric. Page 2 of 2 Agenda Item 5.1 i) Committee Chair’s Report to the Trust Board of Directors 13 January 2026 Committee: Finance, Investment and Cash Committee Meeting Date: 24 November 2025 Key Messages: Assurance: (Reports/Papers reviewed by the Committee also appearing on the Board agenda) Any Other Matters: • The committee received an update in respect of the Trust’s commercial activities, noting that the Trust had robust systems in place to maximise cost recovery for private patient and overseas visitor income. The Trust’s private patient unit project continued to progress. The Trust was also seeking a partner to manage its parking provision. • The committee received the Finance Report for Month 7. The Trust had reported a £5.1m in-month deficit (£35.9m year-to-date), which was in line with the trajectory contained in the Financial Recovery Plan. The underlying deficit remained flat at £6.4m. Whilst there had been a slight reduction in the number of mental health patients, there were c.240 patients having no criteria to reside at any point during the period. There was an increased level of scrutiny in respect of non-pay expenditure. • The committee reviewed an update on the Trust’s measures for financial improvement, noting that the Trust was forecasting achievement of £85-95m against its target of £110m Cost Improvement Programme delivery for 2025/26. • The committee noted the Trust’s approach and the timelines associated with the Medium Term Planning submission. It was noted that the framework set ambitious financial and performance targets. • The committee received an update in respect of the Trust’s Theatre Experience Programme, noting that there had been a 3% increase in utilisation and a 3% reduction in cancellations. • The committee reviewed the Trust’s productivity, noting that the Trust’s productivity had fallen by 3.3% compared to the prior year due to high-cost growth. • The committee received an update in respect of the Trust’s cash position and forecast and supported a proposal to request further cash support for January 2026. • The committee received an update on Capital Planning for 2026/272029/30. It was noted that it was expected that the Trust would be allocated c.£40m per annum, although there were concerns about the impact of the Trust’s cash position and the ability of the Trust to meet this level of expenditure. N/A N/A Page 1 of 2 Assurance Rating: Substantial There is a robust series of suitably designed internal controls in place upon Assurance which the organisation relies to manage the risk of failure of the continuous and effective achievement of the objectives of the process, which at the time of our review were being consistently applied. Reasonable There is a series of controls in place, however there are potential risks that Assurance may not be sufficient to ensure that the individual objectives of the process are achieved in a continuous and effective manner. Improvements are required to enhance the adequacy and effectiveness of the controls to mitigate these risks. Limited Assurance Controls in place are not sufficient to ensure that the organisation can rely upon them to manage the risks to the continuous and effective achievement of the objectives of the process. Significant improvements are required to improve the adequacy and effectiveness of the controls. No Assurance There is a fundamental breakdown or absence of core internal controls such that the organisation cannot rely upon them to manage the risks to the continuous and effective achievement of the objectives of the process. Immediate action is required to improve the adequacy and effectiveness of controls. Not Applicable Where assurance is not required and/or relevant. Risk Rating: Low Medium High Not Applicable Based on the report considered by the committee, there is little or no concern that the Trust will be unable to meet its stated objectives and/or plans. There is some concern that the Trust might not be able to fully meet its stated objectives and/or plans based on the information contained in the report considered by the committee. There is a significant risk that the Trust will not be able to meet its stated objectives and/or plans based on the information contained in the report considered by the committee. Where risk rating is not relevant. Page 2 of 2 Agenda Item 5.1 ii) Committee Chair’s Report to the Trust Board of Directors 13 January 2026 Committee: Finance, Investment and Cash Committee Meeting Date: 15 December 2025 Key Messages: • • • • • • The committee received the Finance Report for Month 8 (see below). The committee discussed the Trust’s future transformation programmes, noting that the areas of focus would be: urgent and emergency care, elective care, and automation of administrative processes. The committee was assured that the programmes were felt to be suitably ‘bold and ambitious’ and were grounded in realistic opportunities, rather than ‘blue sky’ ideas. The committee reviewed the draft capital plan for 2026/27 – 2029/30, noting that the Trust had been allocated c.£40m of capital departmental expenditure limit (CDEL) per year. It was noted that the Trust’s cash position could place constraints on the Trust’s capital programme. The opportunity to secure funding from national programmes outside of CDEL should be pursued vigorously. The plan was to be discussed in a Trust Board Study Session prior to submission in February 2026. The committee reviewed, challenged and discussed the Trust’s medium-term plan ahead of the first submission to NHS England on 17 December 2025. The committee provided feedback in respect of the proposed submission noting that some of the assumptions within the 2025/26 plan had not materialised with regard to matters such as reductions in non-criteria to reside numbers and the committee sought assurance that learnings had been applied to the development of the medium-term plan submission. The committee was assured that such assumed reductions within the 2026/27 plan were based purely on actions which were deemed to be within the Trust’s control. The committee suggested some changes with regard to the plan, particularly around growth assumptions in the cost base, and agreed to recommend the revised plan to the Board for approval. It was noted that more detail and reviews would be required prior to the final submission date in February 2026. The committee received an update in respect of the Trust’s cash position and supported a proposal to make a further request for cash support from NHS England for January 2026. The Trust reviewed and supported a proposal for transforming the Southern Counties Pathology network. Assurance: (Reports/Papers reviewed by the Committee also appearing on the Board agenda) 5.7 Finance Report for Month 8 Assurance Rating: Risk Rating: Substantial High • The Trust had reported an in-month deficit of £4.9m (£40m year-todate), which was consistent with the Trust’s Financial Recovery Plan. • November 2025 had been a challenging month due to costs associated with industrial action, patients with no criteria to reside and mental health patients. • The Trust had received c.£3m of income out of £6.1m for elective over-performance. • There had been a slight improvement in the Trust’s underlying deficit. Page 1 of 2 Any Other N/A Matters: Assurance Rating: Substantial There is a robust series of suitably designed internal controls in place upon Assurance which the organisation relies to manage the risk of failure of the continuous and effective achievement of the objectives of the process, which at the time of our review were being consistently applied. Reasonable There is a series of controls in place, however there are potential risks that Assurance may not be sufficient to ensure that the individual objectives of the process are achieved in a continuous and effective manner. Improvements are required to enhance the adequacy and effectiveness of the controls to mitigate these risks. Limited Assurance Controls in place are not sufficient to ensure that the organisation can rely upon them to manage the risks to the continuous and effective achievement of the objectives of the process. Significant improvements are required to improve the adequacy and effectiveness of the controls. No Assurance There is a fundamental breakdown or absence of core internal controls such that the organisation cannot rely upon them to manage the risks to the continuous and effective achievement of the objectives of the process. Immediate action is required to improve the adequacy and effectiveness of controls. Not Applicable Where assurance is not required and/or relevant. Risk Rating: Low Medium High Not Applicable Based on the report considered by the committee, there is little or no concern that the Trust will be unable to meet its stated objectives and/or plans. There is some concern that the Trust might not be able to fully meet its stated objectives and/or plans based on the information contained in the report considered by the committee. There is a significant risk that the Trust will not be able to meet its stated objectives and/or plans based on the information contained in the report considered by the committee. Where risk rating is not relevant. Page 2 of 2 Agenda Item 5.2 i) Committee Chair’s Report to the Trust Board of Directors 13 January 2026 Committee: People & Organisational Development Committee Meeting Date: 21 November 2025 Key Messages: • • • • The committee reviewed the People Report for Month 7 including progress against the workforce plan. During October 2025, the overall workforce grew by 14 whole-time-equivalents (WTE). Although the substantive workforce had reduced by 15 WTE, there had been lowerthan-expected turnover and increased temporary staffing usage due in part to high sickness levels. The Trust remained on track, however, with respect to its Financial Recovery Plan trajectory. There were concerns about the response rate to the Staff Survey, which was below the national average. The Trust’s vaccination campaign for staff had started well with the uptake rate for the flu vaccine amongst staff at 43%. The committee considered the outputs of the review by NHS England of statutory and mandatory training and the implications for UHS. It was noted that a revised framework would facilitate passporting of training between NHS organisations. The Trust was aligned to the Core Skills Training Framework across six out of eleven areas and ten out of eleven areas for the Utilising E-Learning for Health material. The committee received an update in respect of the Trust’s Inclusion and Belonging strategy. It was noted that resource constraints and the impact of the current financial and operational environment on staff morale had impacted progress towards achievement of the objectives set out in the strategy. The committee reviewed the People risks contained within the Trust’s Board Assurance Framework. Assurance: N/A (Reports/Papers reviewed by the Committee also appearing on the Board agenda) Any Other N/A Matters: Assurance Rating: Substantial There is a robust series of suitably designed internal controls in place upon Assurance which the organisation relies to manage the risk of failure of the continuous and effective achievement of the objectives of the process, which at the time of our review were being consistently applied. Reasonable There is a series of controls in place, however there are potential risks that Assurance may not be sufficient to ensure that the individual objectives of the process are achieved in a continuous and effective manner. Improvements are required to enhance the adequacy and effectiveness of the controls to mitigate these risks. Limited Assurance Controls in place are not sufficient to ensure that the organisation can rely upon them to manage the risks to the continuous and effective achievement of the objectives of the process. Significant improvements are required to improve the adequacy and effectiveness of the controls. Page 1 of 2 No Assurance Not Applicable Risk Rating: Low Medium High Not Applicable There is a fundamental breakdown or absence of core internal controls such that the organisation cannot rely upon them to manage the risks to the continuous and effective achievement of the objectives of the process. Immediate action is required to improve the adequacy and effectiveness of controls. Where assurance is not required and/or relevant. Based on the report considered by the committee, there is little or no concern that the Trust will be unable to meet its stated objectives and/or plans. There is some concern that the Trust might not be able to fully meet its stated objectives and/or plans based on the information contained in the report considered by the committee. There is a significant risk that the Trust will not be able to meet its stated objectives and/or plans based on the information contained in the report considered by the committee. Where risk rating is not relevant. Page 2 of 2 Agenda Item 5.2 ii) Committee Chair’s Report to the Trust Board of Directors 13 January 2026 Committee: People & Organisational Development Committee Meeting Date: 15 December 2025 Key Messages: Assurance: (Reports/Papers reviewed by the Committee also appearing on the Board agenda) • The committee reviewed the People Report for Month 8 (see below) including progress against the workforce plan and Financial Recovery Plan. • The committee considered the workforce implications of the Trust’s medium term plan submission, noting that there were a number of national expectations and targets, such as those relating to sickness rates and elimination of agency spend. In addition, the committee noted the risks associated with the plan, including those where the Trust was reliant on progress with respect to non-criteria to reside and mental health numbers. • The committee received an update regarding the Trust’s Violence and Aggression workstream, noting that the Trust had adopted a revised approach to violence, aggression and abuse directed at staff with a greater willingness to take action against violent/abusive patients and members of the public. A violence and aggression board had been established to provide executive oversight and leadership, and the Trust’s policy was being revised. This work would be accompanied by a comprehensive communication plan for both staff and members of the public. • The committee reviewed the Trust’s progress against its objectives for Year 4 of its People Strategy. 5.9 People Report for Month 8 Assurance Rating: Risk Rating: Substantial High • The overall workforce fell during November 2025, with substantive numbers falling by 52 whole-time-equivalents (WTE). However, temporary staffing use had increased during the month due to increased sickness and operational pressures, which offset much of the reduction in substantive numbers. • The Trust was over its original plan by 214 WTE despite a decrease of nearly 400 WTE since 31 March 2025. In order to hit the Trust’s Financial Recovery Plan target, the overall workforce would need to fall by a further 137 WTE (including a 72 WTE reduction in temporary staffing) by the end of March 2026. • A forecast based on the previous year’s temporary staffing usage for the remaining months of the year indicated that the Trust would end the year approximately 500 WTE above the Trust’s 2025/26 plan. • The Trust had submitted a baseline assessment against the 10 Point Plan to improve Resident Doctors’ working lives in August 2025, which indicated that the Trust compared favourably against other organisations in the South East. The main issues concerned space available for doctors to work in and timeliness of reimbursement of course-related expenses. • The Trust was expected to meet a target of 95% of job plans having been signed off prior to 31 March 2026. At the start of December 2025, 55% of job plans had been signed off. Page 1 of 2 Any Other Matters: • Sickness absence had increased in November 2025 to 4.2% in month due to seasonal illnesses. • The staff survey closed on 28 November 2025. The completion rate for the staff survey had been lower t
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Last updated: 14 September 2019
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