DERBY-BURTON LOCAL CANCER NETWORK FILENAME Lenalidomide_MDS.DOC CONTROLLED DOC NO: HCCPG B78 CSIS Regimen Name: LEN_MDS.

Transcription

1 Lenalidomide Available for Routine Use in Burton in-patient N/A Derby in-patient Burton day-case Derby day-case Burton outreach chemotherapy clinic N/A Derby outreach chemotherapy clinic Burton out-patient Derby out-patient Indication (NICE Approved) Treatment Intent Transfusion-dependent anaemia caused by low or intermediate-1 risk myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate Disease modifying Available ALSO for Use in Not routinely commissioned, each case requires prior documented approval before offering & commencing therapy from either: a) the relevant PCT or b) the relevant SHA Interim Cancer Drugs Fund panel Indication (CDF Approved) Treatment Intent The treatment of myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality where all the following criteria are met: 1. Low or intermediate risk MDS 2. Associated with an isolated deletion 5q cytogenetic abnormality PLUS one additional cytogenetic abnormality 3. Transfusion dependent anaemia (< 8 consecutive weeks without RBC transfusions within 16 weeks prior to commencing treatment) 4. Other therapeutic options insufficient OR inadequate Disease modifying Anti-Emetics Pre-chemotherapy Nil Post-chemotherapy A Day 1 Lenalidomide 10mg Oral ONCE daily (at night) for 21 days (see notes) Frequency & duration: every 28 days until disease relapse or progression REVIEWED BY C.WARD AUTHORISED BY: Dr S Hebballi PAGE 1 of 5

2 Notes: 1. A complete blood cell count, including white blood cell count with differential and platelets should be performed at baseline, every fortnight for the first 8 weeks of lenalidomide treatment and monthly thereafter to monitor for cytopenias. Prescriptions for cycles 1 & 2 will be supported by a fortnightly check of the FBC and toxicities by a Haematology CNS i.e. Patient has a blood test on a Thursday (days 14) Haematology CNS checks FBC and telephones patient to check therapy is being tolerated on a Friday morning Haemtology CNS escalates any problems identified to the treating Consultant 2. Lenalidomide treatment must not be started if the Absolute Neutrophil Counts (ANC) < 0.5 x 10 9 /l and/or platelet counts < 25 x 10 9 /l. 3. Lenalidomide capsules should be taken at about the same time each day. The capsules should not be broken or chewed. The capsules should be swallowed whole, preferably with water, either with or without food. If less than 12 hours has elapsed since missing a dose, the patient can take the dose. If more than 12 hours has elapsed since missing a dose at the normal time, the patient should not take the dose, but take the next dose at the normal time on the following day 4. Thromboprophylaxis In patients with myelodysplatic syndromes, treatment with lenalidomide monotherapy was also associated with a risk of venous thromboembolism (predominantly deep vein thrombosis and pulmonary embolism), but to a lesser extent than in patients with multiple myeloma All patients should receive aspirin unless contraindicated. Patients deemed to be at higher risk eg previous thromboembolic events should receive LMWH. See below Modifiable risk factors for thromboembolic events should be managed wherever possible (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 lenalidomide treatment. 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. Treatment with lenalidomide must be discontinued and anticoagulation therapy started in patients who experience thromboembolic events. Once the patient has been stabilised on anticoagulation treatment and any complications of the REVIEWED BY C.WARD AUTHORISED BY: Dr S Hebballi PAGE 2 of 5

3 thromboembolic event have been managed, lenalidomide may be restarted at the original dose, after a reassessment of risks and benefits of treatment. Anticoagulation should then be continued throughout the course of lenalidomide treatment. 5. Patients with hepatic impairment Lenalidomide has not formally been studied in patients with impaired hepatic function and there are no specific dose recommendations. 6. Patients with Renal Impairment Since lenalidomide is primarily excreted unchanged by the kidney, adjustments should be made to the starting dose of lenalidomide in patients with moderate or severe renal impairment and in patients on dialysis. The recommendations for initial starting doses are : Renal Function (CrCl) Dose Adjustment Moderate renal impairment (30 CrCl < 50 ml/min) Severe renal impairment (CrCl < 30 ml/min, not requiring dialysis) End Stage Renal Disease (ESRD) (CrCl < 30 ml/min, requiring dialysis) On dialysis days, the dose should be administered following dialysis. Cockroft-Gault equation for renal function Females: 1.04 x (140 age) x weight (kg) serum creatinine (micromol/l) 5 mg once daily 2.5 mg once every other day 2.5 mg every other day 2.5 mg twice a week 2.5 mg every other day 2.5 mg twice a week Males: 1.23 x (140 age) x weight (kg) serum creatinine (micromol/l) REVIEWED BY C.WARD AUTHORISED BY: Dr S Hebballi PAGE 3 of 5

4 Side-effects must be closely monitored, particularly thrombocytopenia and neutropenia. Dose reductions may be necessary as outlined overleaf: 7. Suggested Dose Modifications Dose adjustments, as summarized below, are recommended to manage grade 3 or 4 neutropenia or thrombocytopenia, or other grade 3 or 4 toxicity judged to be related to lenalidomide. Dose reduction steps Starting Dose Dose Level -1 Dose Level -2 Dose Level mg once daily on days 1-21 every 28 days 5 mg once daily on days 1-28 every 28 days on days 1-28 every 28 days 2.5 mg every other day 1-28 every 28 days For patients who are dosed initially at 10 mg and who experience thrombocytopenia or neutropenia: Thrombocytopenia When platelets Fall to < 25 x 10 9 /l Return to 25 x 10 9 /l - < 50 x 10 9 /l on at least 2 occasions for 7 days or when the platelet count recovers to 50 x 10 9 /l at any time Recommended Course Interrupt lenalidomide treatment Resume lenalidomide at next lower dose level (Dose Level -1, -2 or -3) Neutropenia When neutrophils Fall to < 0.5 x 10 9 /l Return to 0.5 x 10 9 /l Recommended Course Interrupt lenalidomide treatment Resume lenalidomide at next lower dose level (Dose Level -1, -2 or -3) For patients who experience other toxicities For other grade 3 or 4 toxicities judged to be related to lenalidomide, stop treatment and restart at next lower dose level when toxicity has resolved to grade 2 depending on the physician's discretion. Lenalidomide interruption or discontinuation should be considered for grade 2 or 3 skin rash. Lenalidomide must be discontinued for angioedema, grade 4 rash, exfoliative or bullous rash, or if Stevens-Johnson syndrome or toxic epidermal necrolysis is suspected, and should not be resumed following discontinuation from these reactions. REVIEWED BY C.WARD AUTHORISED BY: Dr S Hebballi PAGE 4 of 5

5 8. Discontinuation of lenalidomide Patients without at least a minor erythroid response within 4 months of therapy initiation, demonstrated by at least a 50% reduction in transfusion requirements or, if not transfused, a 1g/dl rise in haemoglobin, should discontinue lenalidomide treatment. 9. Lenalidomide is structurally related to thalidomide which is a known human teratogen. Prescibing of lenalidomide must be in line with the conditions of the Pregnancy Prevention Programme. A prescription authorisation form must be completed with each prescription for lenalidomide and be sent to pharmacy with the prescription chart References: 1. Celgene; Summary of Product Characteristics - Document last updated on the emc: 25-Nov-2014 (accessed 10/2/2015) 2. NICE technology appraisal guidance [TA322] Lenalidomide for treating myelodysplastic syndromes associated with an isolated deletion 5q cytogenetic abnormality - Published date: September 2014 REVIEWED BY C.WARD AUTHORISED BY: Dr S Hebballi PAGE 5 of 5