FDA approves lenalidomide oral capsules (Revlimid) for use in combination with dexamethasone in patients with multiple myeloma

On June 29, 2006, the U.S. Food and Drug Administration granted approval to lenalidomide oral capsules (Revlimid, Celgene Corporation) for use in combination with dexamethasone in patients with multiple myeloma who have received one prior therapy.  Revlimid is available under a special restricted distribution program, called RevAssist (described below).

Efficacy and safety were demonstrated in two randomized, double-blind, multi-center, multi-national, placebo-controlled studies comparing the combination of lenalidomide plus oral pulse dexamethasone versus dexamethasone alone in patients with multiple myeloma who had received at least one prior therapy. Revlimid (lenalidomide) was administered at a starting dose of 25 mg/day orally as a single 25 mg capsule on days 1‑21 of repeated 28-day cycles. Dexamethasone was administered orally at a dose of 40 mg/day on days 1‑4, 9‑12, and 17‑20 of each 28‑day cycle for the first 4 cycles and then 40 mg/day orally on days 1‑4 every 28 days in both treatment arms of both studies.

Data were evaluated from 692 patients in the two studies, 341 patients in Study 1 and 351 patients in Study 2. The primary endpoint of time-to-progression (TTP) was evaluated in a pre-specified interim analysis in each study.  In Study 1, median TTP was 37.1 weeks in the lenalidomide/dexamethasone arm compared to 19.9 weeks with dexamethasone alone (HR=0.356; 95% CI [0.257, 0.494]; p < 0.0001).  In Study 2, median TTP was not reached in the lenalidomide/dexamethasone arm compared to 20 weeks in the dexamethasone alone arm (HR=0.392; 95% CI [0.274, 0.562]; p < 0.0001).

Safety data were evaluated from 691 patients in the two studies. Grade 3 and 4 neutropenia, thrombocytopenia, leukopenia, lymphopenia, febrile neutropenia, deep vein thrombosis, pulmonary embolism, atrial fibrillation, constipation, diarrhea, fatigue, pneumonia, hypokalemia, hypocalcemia, muscle weakness, neuropathy and depression were reported in a greater proportion of patients treated with the combination of lenalidomide and dexamethasone compared to dexamethasone alone.

Thrombotic or thromboembolic events, including deep vein thrombosis, pulmonary embolism, thrombosis, and intracranial venous sinus thrombosis were reported more frequently in patients treated with the combination of lenalidomide plus dexamethasone (12%) compared to dexamethasone alone (4%) in the pooled analyses.  Patients and physicians are advised to be observant for the signs and symptoms of thromboembolism. It is unknown whether prophylactic anticoagulation or antiplatelet therapy prescribed in conjunction with lenalidomide may reduce the potential for venous thromboembolic events. The decision to prescribe prophylactic measures should be considered carefully after an assessment of an individual patient's underlying risk factors.

Patients with renal impairment were excluded from the studies. Because lenalidomide is primarily excreted by the kidney, renal function should be carefully monitored.

Females should be advised to avoid pregnancy while taking lenalidomide. Lenalidomide is an analogue of thalidomide, a known human teratogen that causes severe life-threatening human birth defects. Reproductive toxicity studies are ongoing to assess lenalidomide's potential teratogenicity. To avoid fetal exposure, lenalidomide is only available under a special restricted distribution program called RevAssist. Under this program, only prescribers and pharmacists registered with the program can prescribe and dispense the product.  Patients enrolled in the program to receive the drug must agree to comply with the requirements of the RevAssist program. 

Full prescribing information including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at www.fda.gov/cder/foi/label/2005/021880lbl.pdf.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA's MedWatch Reporting System by phone at 1-800-FDA-1088; by facsimile 1-800-FDA-0178 by mail using the Form 3500 at http://www.fda.gov/medwatch.index.html.

For further information related to oncology drug approvals, regulatory information, and other oncology resources, please refer to the FDA “Oncology Tools” website at www.fda.gov/cder/cancer.

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