FDA Expands Revlimid Label

Treatment approved for post-HSCT maintenance in multiple myeloma patients

The FDA has expanded the existing indications for lenalidomide (Revlimid, Celegen Corporation), a thalidomide analogue, to include use in patients with multiple myeloma as maintenance therapy after autologous hematopoietic stem-cell transplant (auto-HSCT). The expanded indication makes lenalidomide the only treatment to receive FDA approval for maintenance use following auto-HSCT.

The approval was based on results from two large studies that compared lenalidomide maintenance therapy––given until disease progression or unacceptable toxicity occurred––with no maintenance therapy after auto-HSCT in more than 1,000 patients. In both studies, the primary efficacy endpoint was progression-free survival (PFS), defined as survival from randomization to the date of progression or death, whichever occurred first.

Study 1 (a U.S.-based, National Cancer Institute-sponsored trial) demonstrated median PFS of 5.7 years with lenalidomide maintenance therapy compared with 1.9 years without maintenance, for a difference of 3.8 years (hazard ratio [HR]: 0.38).

Study 2 (a European-based trial) also showed a clinical benefit, with median PFS of 3.9 years with lenalidomide maintenance therapy compared with 2.0 years without maintenance, for a difference of 1.9 years (HR: 0.53).

Neither study was powered for an endpoint of overall survival (OS). A descriptive analysis showed, however, that median OS in Study 1 was 9.3 years for patients who received lenalidomide maintenance therapy compared with 7.0 years for those who did not (HR: 0.59). In Study 2, median OS was 8.8 years for the group with maintenance therapy compared with 7.3 years for the group without maintenance (HR: 0.90).

Hematologic second primary malignancies (SPMs) occurred in 7.5% of patients receiving lenalidomide maintenance therapy compared with 3.3% of patients receiving placebo. The rates of hematologic plus solid-tumor SPMs (excluding squamous cell carcinoma and basal cell carcinoma) was 14.9% compared with 8.8%, respectively, during a median follow-up period of 91.5 months. Nonmelanoma skin-cancer SPMs, including squamous cell carcinoma and basal cell carcinoma, occurred in 3.9% of patients receiving lenalidomide maintenance compared with 2.6% in the placebo arm. Clinicians should monitor patients for the development of SPMs and should consider both potential benefits and the risk of SPMs when considering treatment with lenalidomide.

Lenalidomide in combination with dexamethasone was approved in June 2006 for patients with multiple myeloma who have received at least one prior therapy. It is also indicated for patients with transfusion-dependent anemia due to low- or intermediate-1–risk myelodysplastic syndromes (MDS) associated with a deletion 5q abnormality with or without additional cytogenetic abnormalities, and for patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib. Lenalidomide is not indicated or recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials.

Sources: Celgene; February 22, 2017; and Revlimid Prescribing Information; February 2015.