On May 28, 2019, the FDA approved lenalidomide (Revlimid; Celgene), in combination with rituximab (Rituxan), for the treatment of patients with previously treated follicular lymphoma or marginal-zone lymphoma (MZL). The FDA used its priority review program for this approval, and granted lenalidomide plus rituximab an orphan drug designation for this new indication.
Lenalidomide was previously approved for several hematologic malignancies, and was initially approved in 2005 for patients with transfusion-dependent anemia that resulted from low- or intermediate-1–risk myelodysplastic syndromes associated with 5q deletion, with or without additional cytogenetic abnormalities.
This new indication was based on the results of 2 clinical trials. The AUGMENT study included 358 patients with relapsed or refractory follicular lymphoma or MZL who were randomized in a 1:1 ratio to lenalidomide plus rituximab or to placebo plus rituximab. The single-arm MAGNIFY trial included 232 patients with relapsed or refractory follicular lymphoma, MZL, or mantle-cell lymphoma who received 12 induction cycles of lenalidomide plus rituximab. The primary end point of the AUGMENT trial was progression-free survival (PFS), as determined by an Independent Review Committee (IRC).
The median PFS was 39.4 months (95% confidence interval [CI], 22.9-not estimable) with lenalidomide plus rituximab versus 14.1 months (95% CI, 11.4-16.7) with placebo plus rituximab. The overall response rate (ORR) by IRC assessment was 80% in the lenalidomide arm versus 55.4% with placebo in patients with follicular lymphoma, and 65% versus 44%, respectively, in patients with MZL.
In the MAGNIFY trial, the ORR was 59% (95% CI, 51-66) in patients with follicular lymphoma and 51% (95% CI, 36-66) in patients with MZL. The median duration of response has not been reached in either patient population.
The most common (≥20%) adverse events associated with lenalidomide in both clinical trials were neutropenia, fatigue, diarrhea, constipation, nausea, and cough. The prescribing information also carries a boxed warning about the risk for embryo-fetal toxicity, hematologic toxicity, and venous and arterial thromboembolism.