ASH News Daily 2013 - Day 2 - (Page B-11)

Venous Thromboembolism: Venous thromboembolic events (predominantly deep venous thrombosis and pulmonary embolism) have occurred in patients with MCL treated with lenalidomide monotherapy. It is not known whether prophylactic anticoagulation or antiplatelet therapy prescribed in conjunction with REVLIMID may lessen the potential for venous thromboembolism. The decision to take prophylactic measures should be done carefully after assessment of the individual patient's underlying risk factors. Allergic Reactions: Angioedema and serious dermatologic reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported. These events can be fatal. Patients with a prior history of Grade 4 rash associated with thalidomide treatment should not receive REVLIMID. REVLIMID interruption or discontinuation should be considered for Grade 2-3 skin rash. REVLIMID must be discontinued for angioedema, Grade 4 rash, exfoliative or bullous rash, or if SJS or TEN is suspected and should not be resumed following discontinuation for these reactions. REVLIMID capsules contain lactose. Risk-benefit of REVLIMID treatment should be evaluated in patients with lactose intolerance. Tumor Lysis Syndrome: Fatal instances of tumor lysis syndrome (TLS) have been reported during treatment with lenalidomide. The patients at risk of TLS are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken. Tumor Flare Reaction: Tumor flare reaction (TFR) occurred during investigational use of lenalidomide for chronic lymphocytic leukemia (CLL) and lymphoma, and is characterized by tender lymph node swelling, low grade fever, pain and rash. Treatment of CLL with lenalidomide outside of a well-monitored clinical trial is discouraged. Monitoring and evaluation for TFR is recommended in patients with MCL. Tumor flare may mimic the progression of disease (PD). In patients with Grade 3 or 4 TFR, it is recommended to withhold treatment with lenalidomide until TFR resolves to ≤ Grade 1. In the MCL trial, approximately 10% of subjects experienced TFR; all reports were Grade 1 or 2 in severity. All of the events occurred in cycle 1 and one patient developed TFR again in cycle 11. Lenalidomide may be continued in patients with Grade 1 and 2 TFR without interruption or modification, at the physician's discretion. Patients with Grade 1 or 2 TFR may also be treated with corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and/or narcotic analgesics for management of TFR symptoms. Patients with Grade 3 or 4 TFR may be treated for management of symptoms per the guidance for treatment of Grade 1 and 2 TFR. Hepatotoxicity: Hepatic failure, including fatal cases, has occurred in patients treated with lenalidomide in combination with dexamethasone. The mechanism of drug-induced hepatotoxicity is unknown. Pre-existing viral liver disease, elevated baseline liver enzymes, and concomitant medications may be risk factors. Monitor liver enzymes periodically. Stop Revlimid upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered. Second Primary Malignancies: Patients with MM treated with lenalidomide in studies including melphalan and stem cell transplantation had a higher incidence of second primary malignancies, particularly acute myelogenous leukemia (AML) and Hodgkin lymphoma, compared to patients in the control arms who received similar therapy but did not receive lenalidomide. Monitor patients for the development of second malignancies. Take into account both the potential benefit of lenalidomide and the risk of second primary malignancies when considering treatment with lenalidomide. ADVERSE REACTIONS Mantle Cell Lymphoma * Grade 3 and 4 adverse events reported in ≥5% of patients treated with REVLIMID in the MCL trial (N=134) included neutropenia (43%), thrombocytopenia (28%), anemia (11%), pneumonia (9%), leukopenia (7%), fatigue (7%), diarrhea (6%), dyspnea (6%), and febrile neutropenia (6%) * Serious adverse events reported in ≥2 patients treated with REVLIMID monotherapy for MCL included chronic obstructive pulmonary disease, clostridium difficile colitis, sepsis, basal cell carcinoma, and supraventricular tachycardia * Adverse events reported in ≥15% of patients treated with REVLIMID in the MCL trial included neutropenia (49%), thrombocytopenia (36%), fatigue (34%), anemia (31%), diarrhea (31%), nausea (30%), cough (28%), pyrexia (23%), rash (22%), dyspnea (18%), pruritus (17%), peripheral edema (16%), constipation (16%), and leukopenia (15%) * Adverse events occurring in patients treated with REVLIMID in the MCL trial resulted in at least one dose interruption in 76 (57%) patients, at least one dose reduction in 51 (38%) patients, and discontinuation of treatment in 26 (19%) patients DRUG INTERACTIONS Periodic monitoring of digoxin plasma levels, in accordance with clinical judgment and based on standard clinical practice in patients receiving this medication, is recommended during administration of REVLIMID. USE IN SPECIFIC POPULATIONS Pregnancy: If pregnancy does occur during treatment, immediately discontinue the drug. Under these conditions, refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. Any suspected fetal exposure to REVLIMID must be reported to the FDA via the MedWatch program at 1-800-332-1088 and also to Celgene Corporation at 1-888-423-5436. Nursing Mothers: It is not known whether REVLIMID is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother. Pediatric Use: Safety and effectiveness in pediatric patients below the age of 18 have not been established. Geriatric Use: Since elderly patients are more likely to have decreased renal function, care should be taken in dose selection. Monitor renal function. Renal Impairment: Since REVLIMID is primarily excreted unchanged by the kidney, adjustments to the starting dose of REVLIMID are recommended to provide appropriate drug exposure in patients with moderate (CLcr 30-60 mL/min) or severe renal impairment (CLcr <30 mL/min) and in patients on dialysis. Please see Brief Summary of full Prescribing Information, including Boxed WARNINGS, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS, on the following pages. 

Table of Contents for the Digital Edition of ASH News Daily 2013 - Day 2

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ASH News Daily 2013 - Day 2

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