R-BAC-500 (Rituximab, Bendamustine, Cytarabine) for Mantle Cell Lymphoma

Transcription

1 R-BAC-500 (Rituximab, Bendamustine, Cytarabine) for Mantle Cell Lymphoma Not routinely commissioned, each case requires prior documented approval before offering & commencing therapy from NHS England Cancer Drug Fund Indication 1. 1 st line in patients considered unsuitable for standard treatment. See NHS England CDF cohort list for further details OR Available for routine use in Indication Relapsed Mantle Cell Lymphoma in patients considered unsuitable for standard treatment. Treatment Intent Palliative Anti-Emetics Pre-chemotherapy 3 Post-chemotherapy C plus Ondansetron 8mg TWICE daily for 5 days Blood Products Irradiated blood products required lifelong- inform blood bank. Frequency & Duration Every 28 days for a maximum of 6 cycles (assess response after cycle 2). In cycle 1, Rituximab is given either as a single dose or as a split dose, or may be omitted at the clinicians discretion. Please see notes below for further information on which type of dose to administer. Cycle 1- Single dose Rituximab Day 1 Prednisolone 100mg Oral 30 minutes prior to Chlorphenamine 10mg Intravenous bolus 30 minutes prior to Hydrocortisone 100mg Intravenous bolus 30 minutes prior to Paracetamol 1g Oral 30 minutes prior to Rituximab 375mg/m 2 Intravenous infusion in 500ml sodium chloride 0.9% using first infusion rate Pethidine 25mg Intravenous bolus STAT if required for febrile infusion reaction Allopurinol 300mg Oral once daily for 2 weeks (reduce dose in renal impairment) Cotrimoxazole 480mg Oral once daily for 28 days Aciclovir 400mg Oral twice daily for 28 days Day 2 Ondansetron 8mg Oral twice daily for 5 days Dexamethasone 8mg Oral as a single dose prior to bendamustine REVIEWED BY: K.GRAHAM AUTHORISED BY: Dr J Addada PAGE 1 of 9

2 Bendamustine 70mg/m 2 Intravenous infusion in 500ml sodium chloride 0.9% over minutes Metoclopramide 10mg Oral four times daily for 4 days, and then as required Prednisolone (Predsol 0.5%) 1 drop Eye drops 4 times daily in each eye for 3 days Day 3 Dexamethasone 8mg Oral as a single dose prior to bendamustine Bendamustine 70mg/m 2 Intravenous infusion in 500ml sodium chloride 0.9% over minutes Day 4 Dexamethasone 8mg Oral as a single dose prior to cytarabine Day 7 Dexamethasone 4mg Oral twice daily for 2 days Filgrastim biosimilar Or Cycle 1- Split dose Rituximab 300micrograms Subcutaneous injection ONCE daily on days 7, 9,11,13,15 Day 1 Prednisolone 100mg Oral 30 minutes prior to Chlopheniramine 10mg Intravenous bolus 30 minutes prior to Hydrocortisone 100mg Intravenous bolus 30 minutes prior to Paracetamol 1g Oral 30 minutes prior to Rituximab 100mg Intravenous infusion in 100ml sodium chloride 0.9% over 4 hours Pethidine 25mg Intravenous bolus stat if required for febrile infusion reaction Allopurinol 300mg Oral once daily for 2 weeks (reduce dose in renal impairment) Cotrimoxazole 480mg Oral once daily for 28 days Aciclovir 400mg Oral twice daily for 28 days Day 2 Chlorphenamine 10mg Intravenous bolus 30 minutes prior to Hydrocortisone 100mg Intravenous bolus 30 minutes prior to Paracetamol 1g Oral 30 minutes prior to Prednisolone 100mg Oral 30 minutes prior to REVIEWED BY: K.GRAHAM AUTHORISED BY: Dr J Addada PAGE 2 of 9

3 Rituximab 375mg/m 2 minus 100mg (i.e. remainder of dose) If severe (grade 2 or above) reaction on day 1. Intravenous infusion in 500ml sodium chloride 0.9% using first infusion rate Pethidine 25mg Intravenous bolus STAT if required for infusion reaction Ondansetron 8mg Oral twice daily for 5 days Dexamethasone 8mg Oral as a single dose (not required if had prednisolone dose above) Bendamustine 70mg/m 2 Intravenous infusion in 500ml 0.9% sodium chloride over minutes Prednisolone (Predsol 0.5%) 1 drop Eye drops 4 times daily in each eye for 3 days Metoclopramide 10mg Oral four times daily for 4 days, and then as required Day 3 Dexamethasone 8mg Oral as a single dose prior to bendamustine Bendamustine 70mg/m 2 Intravenous infusion in 500ml 0.9% sodium chloride over minutes Day 4 Dexamethasone 8mg Oral as a single dose prior to cytarabine Dexamethasone 4mg Oral twice daily for 2 days Day 7 Filgrastim biosimilar Cycle 2 onwards 300micrograms Subcutaneous injection ONCE daily on days 7, 9,11,13,15 Day 1 Prednisolone 100mg Oral 30 minutes prior to If severe (grade 2 or above) reaction at prior cycle Chlorphenamine 10mg Intravenous bolus 30 minutes prior to Hydrocortisone 100mg Intravenous bolus 30 minutes prior to Paracetamol 1g Oral 30 minutes prior to Rituximab 375mg/m 2 Intravenous infusion in 500ml sodium REVIEWED BY: K.GRAHAM AUTHORISED BY: Dr J Addada PAGE 3 of 9

4 chloride 0.9% using first infusion rate Pethidine 25mg Intravenous bolus STAT if required for febrile infusion reaction Allopurinol 300mg Oral once daily for 2 weeks (reduce dose in renal impairment) Cotrimoxazole 480mg Oral once daily for 28 days Aciclovir 400mg Or Oral twice daily for 28 days Day 2 Ondansetron 8mg Oral twice daily for 5 days Dexamethasone 8mg Oral as a single dose prior to bendamustine Bendamustine 70mg/m 2 Intravenous infusion in 500ml sodium chloride 0.9% over minutes Prednisolone (Predsol 0.5%) 1 drop Eye drops 4 times daily in each eye for 3 days Metoclopramide 10mg Oral four times daily for 4 days, and then as required Day 3 Dexamethasone 8mg Oral as a single dose prior to bendamustine Bendamustine 70mg/m 2 Intravenous infusion in 500ml sodium chloride 0.9% over minutes Day 4 Dexamethasone 8mg Oral as a single dose prior to cytarabine Dexamethasone 4mg Oral twice daily for 2 days Day 7 Filgrastim biosimilar 300micrograms Subcutaneous injection ONCE daily on days 7, 9,11,13,15 REVIEWED BY: K.GRAHAM AUTHORISED BY: Dr J Addada PAGE 4 of 9

5 Notes: All patients who receive bendamustine should receive irradiated blood products throughout their chemotherapy and for life. Inform Blood bank. The risk of cytokine release syndrome is increased when the peripheral blood lymphocyte count is greater than 30-50x10 9 /l. Clinicians may wish to premedicate patients with high tumour burden with steroids prior to the 1 st cycle or omit the Rituximab from the 1st cycle of treatment. Baseline tests: FBC, U&Es, LFTs, calcium, phosphate, urate. Hep B&C, CMV, HIV ECG+/- Echo if clinically indicated Tests before each cycle: FBC, U&Es, LFTs. Calcium, phosphate, urate as clinically indicated. Drug interactions Tumour lysis syndrome associated with bendamustine treatment has been reported in patients in clinical trials. The onset tends to be within 48 hours of the first dose of bendamustine. The use of allopurinol during the first one to two weeks of bendamustine may be considered. However, there have been a few cases of Stevens-Johnson syndrome and toxic epidermal necrolysis reported when bendamustine and allopurinol are administered concomitantly. Clinicians may consider omitting allopurinol on the days of bendamustine for patients at low risk of tumour lysis syndrome. Bendamustine metabolism involves the cytochrome P450 (CYP) 1A2 isoenzyme. Therefore, the potential for interaction with CYP1A2 inhibitors such as fluvoxamine, ciprofloxacin, aciclovir and cimetidine exists. Dose modifications and toxicities 1. Haematological toxicity Neutropenia and thrombocytopenia may be due to disease. However, if any fall in counts is thought to be due to treatment the following guidelines should be followed: Neutrophils <1.0x 10 9 /l or Platelets <75 x 10 9 /l Delay until neutrophils >1.0x 10 9 /l and platelets >75 x 10 9 /l and give ALL subsequent cycles at 75% dose. If counts haven t recovered after 2 weeks delay, withdraw from treatment. REVIEWED BY: K.GRAHAM AUTHORISED BY: Dr J Addada PAGE 5 of 9

6 2. Renal impairment Bendamustine: No dose adjustment is necessary in patients with a creatinine clearance of >10 ml/min. Experience in patients with severe renal impairment is limited. Cytarabine: GFR ml/min Cytarabine dose >60 100% % % <30 contraindicated 1. Hepatic impairment Bendamustine: Bilirubin micromol/l Dose <20 100% % >51 No data available * *No data is available in patients with severe hepatic impairment (serum bilirubin values of > 51 micromol/l). Cytarabine: If bilirubin >34 micromol/l give 50% dose cytarabine. Consider subsequent dose escalation in the absence of toxicity. REVIEWED BY: K.GRAHAM AUTHORISED BY: Dr J Addada PAGE 6 of 9

7 4. Infusion related reactions Infusion reactions to bendamustine hydrochloride have occurred commonly in clinical trials. Symptoms are generally mild and include fever, chills, pruritus and rash. In rare instances severe anaphylactic and anaphylactoid reactions have occurred. Patients must be asked about symptoms suggestive of infusion reactions after their first cycle of therapy (see Table below) Pre-medication with antihistamine (e.g. chlorphenamine 4mg oral or 10mg intravenous), paracetamol (1g oral) and steroid (e.g. dexamethasone 8mg oral or intravenous or hydrocortisone 100mg intravenous) should be considered with subsequent cycles for patients who experience even a mild hypersensitivity reaction on cycle 1. It is suggested that reactions Grade 3 should not be rechallenged. NCI CTC Allergic reaction score Grade None Transient rash, fever <38 C Anaphylaxis Urticaria, fever>38 C and/or asymptomatic bronchospasm Symptomatic bronchospasm requiring parenteral medication without urticaria; allergy related angioedema/ oedema 5. Cytarabine toxicities Cytosine syndrome is characterised by fever, myalgia, bone pain, occasional chest pains, maculopapular rash, conjunctivitis and malaise. This usually occurs 6-12 hours following infusion, and is more common with higher doses. Systemic steroids have been beneficial in treating this condition if severe.cerebral and cerebellar toxicity can cause significant and varied neurological manifestations but are usually reversible. 6. Patients with cardiac disorders During treatment with bendamustine hydrochloride the concentration of potassium in the blood must be closely monitored and potassium supplements must be given when K + <3.5 mmol/l, and ECG measurement must be performed REVIEWED BY: K.GRAHAM AUTHORISED BY: Dr J Addada PAGE 7 of 9

8 Rituximab This section should be read in conjunction with the Guidelines for the administration of Rituximab. Patients with low grade NHL may be at particularly high risk of severe reactions during infusion due to cytokine release syndrome. Accordingly patients should be treated with extreme caution. A split dose of should be given in cycle 1 if the WBC is > 25 x 10 9 /l or bulky disease is present. Close monitoring during the infusion is required. 1. Premedication consisting of analgesia and an antihistamine and an intravenous corticosteroid should always be administered 30 minutes before each infusion of. (e.g. paracetamol 1g oral STAT and chlorphenamine 4mg oral or 10mg IV bolus STAT and hydrocortisone 100mg IV STAT). In addition pethidine 25mg IV should be available in case of a severe infusion reaction. Premedication consisting of 100mg prednisolone orally given 30 minutes before should be given on cycle 1 in addition to the normal premedication listed above. This should be repeated on Day 2 of cycle 1 where a split dose is given. If the patient develops a severe febrile reaction to, consider giving 100mg prednisolone prior to in subsequent cycles. 2. Rituximab doses should be rounded to the nearest 100mg. Use rate calculator to assist with rate escalation of infusion. Infusion rates for should be as follows: All patients having split dose in Cycle 1 will have day one at 25 mg/hr (i.e.100mg over 4 hours) followed by the remainder on day 2 at the first infusion rate. Cycle 2 will be given by the licensed approach. Only when the patient has successfully received a full dose of at the licensed rate should infusion by the rapid rate be considered. 3. Occurrence of an Infusion Related Event or Hypersensitivity Stop the infusion and contact a doctor. When symptoms improve, continue the infusion at half the rate prior to the reaction. Accelerate the infusion rate more slowly as tolerated by the patient. REVIEWED BY: K.GRAHAM AUTHORISED BY: Dr J Addada PAGE 8 of 9

9 Supportive care Patients at risk of tumour lysis syndrome must receive prophylaxis prior to initiation of treatment. Refer to tumour lysis syndrome guidelines. All patients should receive Pneumocystis jirovecii & antiviral prophylaxis throughout treatment and for at least 6 months or until the lymphocyte count is >1.0 x 10 9 /l. Co-trimoxazole 480mg ONCE daily. In cases of allergy to co-trimoxazole, consider dapsone 100mg daily. Aciclovir 400mg twice daily. Prednisoline 0.5% eye drops for the prevention of cytarabine-induced conjunctivitis. The duration is restricted to the days of active treatment with cytarabine but may be continued for 5 days beyond this if symptoms persist. References 1. Summary of Product Characteristics last updated on the emc: 10/08/2010 (Accessed 3/5/2011) 2. Rituximab, bendamustine and low-dose cytarabine as induction therapy in elderly patients with mantle cell lymphoma: a multicentre, phase 2 trial from Fondazione Italiana Linfomi. Carlo Visco et al. The Lancet Haematology 2017; 4:e15-e UCLH-Doasge Adjustment for Cytotoxics in Hepatic Impairment (Jan 2009) 4. UCLH-Doasge Adjustment for Cytotoxics in Renal Impairment (Jan 2009) REVIEWED BY: K.GRAHAM AUTHORISED BY: Dr J Addada PAGE 9 of 9