On June 5, 2013, the U. S. Food and Drug Administration approved lenalidomide capsules (REVLIMID, Celgene Corporation), for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib.
The approval was based a single-arm, multicenter clinical trial enrolling 134 patients with mantle cell lymphoma who have relapsed after or were refractory to bortezomib or a bortezomib-containing regimen. All 134 patients received prior treatment with bortezomib and 60% were documented to have disease refractory to bortezomib therapy. Patients received a median of 4 prior therapies for MCL. The median age was 67 years, 81% were male, 96% were Caucasian, and 61% had MCL for at least 3 years.
The efficacy endpoints were overall response rate (ORR) and duration of response (DOR). The ORR was defined as the proportion of patients whose best response was complete response (CR), complete response unconfirmed (CRu), or partial response (PR). In the 133 patients who were evaluable for efficacy, the ORR was 26% (95% CI: 18.4, 33.9). CR or CRu was achieved by 9 patients (7%) and 25 patients (19%) achieved a PR. The median DOR for the 34 patients who achieved a CR, CRu, or PR was 16.6 months (95% CI: 7.7, 26.7).
Safety data was evaluated in 134 patients who received at least one dose of lenalidomide. The median duration of therapy was 95 days (range 1-1002) and 78 (58%) of patients received 3 or more cycles of therapy. Seventy-six patients (57%) underwent at least one dose interruption due to adverse events and 51 patients (38%) underwent at least one dose reduction due to adverse events. Twenty-six patients (19%) discontinued treatment due to adverse events.
The most common (≥15%) grade 1-4 adverse reactions included neutropenia, thrombocytopenia, fatigue, anemia, diarrhea, nausea, cough, pyrexia, rash, dyspnea, pruritis, constipation, peripheral edema and leukopenia. The most common (≥ 5%) grade 3-4 adverse reactions were neutropenia, thrombocytopenia, anemia, pneumonia, leukopenia, fatigue, febrile neutropenia, dyspnea and diarrhea.
The recommended dose and schedule for lenalidomide is 25 mg orally once daily on days 1-21 of repeated 28-day cycles. Lenalidomide should be taken at about the same time each day, either with or without food.
This supplemental application also included the approval of a new 20 mg capsule strength.
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 completing a form online at http://www.fda.gov/medwatch/report.htm
, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).