FDA Approves Front-Line Lenalidomide for Multiple Myeloma

The FDA has expanded the use of oral lenalidomide in multiple myeloma to include its use in combination with dexamethasone for newly diagnosed patients.

The US Food and Drug Administration (FDA) has expanded the use of oral lenalidomide in patients with multiple myeloma to include its use in combination with dexamethasone for patients with newly diagnosed disease.

The approval is based on the results of several phase III studies that evaluated lenalidomide plus dexamethasone in comparison with the current standard-of-care melphalan, prednisone, and thalidomide (MPT), including the FIRST trial (MM-020/IFM 07-01).

Results of the FIRST trial were presented in December 2013 at the 2013 American Society of Hematology (ASH) Annual Meeting and Exposition. In the study, 1,623 patients with newly diagnosed multiple myeloma were randomly assigned to treatment with lenalidomide plus low-dose dexamethasone given continuously, the same combination given for 18 cycles for 18 months, or to MPT.

Results of the study showed that patients assigned to continuous treatment with lenalidomide/dexamethasone had a 28% reduced risk for disease progression, with a median progression-free survival of 25.5 months compared with 21.2 months for those assigned MPT (hazard ratio [HR] = 0.72; P = .0001). Based on data from a March 2014 analysis, patients assigned lenalidomide had a 25% reduced risk for death compared with MPT. The median overall survival was 58.9 months for patients assigned lenalidomide/dexamethasone compared with 48.5 months for MPT (HR = 0.75; 95% confidence interval [CI], 0.62–0.90).

Grade 3 or 4 adverse events frequently reported in patients assigned continuous lenalidomide/dexamethasone were neutropenia (27.8%), anemia (18.2%), thrombocytopenia (8.3%), pneumonia (11.3%), asthenia (7.7%), fatigue (7.3%), back pain (7%), hypokalemia (6.6%), rash (7.3%), cataract (5.8%), dyspnea (5.6%), deep vein thrombosis (5.6%), and hyperglycemia (5.3%).

Lenalidomide is currently approved for three disease states. In December 2005, lenalidomide was first approved for use in patients with transfusion-dependent anemia due to low- or intermediate-risk myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. In June 2006, the drug was granted approval for patients with multiple myeloma who had received one prior therapy. Finally, in June 2013, the FDA approved lenalidomide for treatment of mantle cell lymphoma in patients whose disease had relapsed or progressed after two prior therapies, one of which included bortezomib.