The U.S. Food and Drug Administration (FDA) has expanded the existing indication for lenalidomide (Revlimid) in combination with dexamethasone to include patients newly diagnosed with multiple myeloma. Lenalidomide plus dexamethasone was previously approved in June 2006 for use in multiple myeloma patients who have received at least one prior therapy.
“The approval of [lenalidomide] as an option for use in all patients with multiple myeloma represents a new paradigm in the management of this disease,” said Kenneth Anderson, MD, Director, Jerome Lipper Multiple Myeloma Center, Dana-Farber/Brigham and Women’s Cancer Center. “We now have clinical evidence demonstrating that starting and keeping newly diagnosed multiple myeloma patients on [lenalidomide] significantly improves progression-free survival.”
Phase III Study Results
The approval was based on safety and efficacy results from phase III studies, including the FIRST trial, which evaluated continuous lenalidomide in combination with dexamethasone until disease progression vs melphalan, prednisone, and thalidomide (Thalomid) for 18 months as the primary analysis, and a fixed duration of 18 cycles of continuous lenalidomide plus dexamethasone as a secondary analysis, in 1,623 newly diagnosed patients who were not candidates for stem cell transplant. The primary endpoint of this randomized, open-label, three-arm trial was median progression-free survival.
Progression-free survival was significantly longer for patients receiving continuous lenalidomide plus dexamethasone (25.5 months) than for those treated with melphalan, prednisone, and thalidomide (21.2 months; hazard ratio [HR] = 0.72, P = .0001). Median overall survival in the two groups was 58.9 months and 48.5 months, respectively (HR = 0.75, 95% confidence interval = 0.62–0.90) based on a March 3, 2014, interim overall survival analysis. Patients in the lenalidomide-plus-dexamethasone arm had a 25% reduction in the risk of death compared with patients who received melphalan, prednisone, and thalidomide.
Safety results showed that adverse reactions reported in ≥ 20% of patients included diarrhea, anemia, neutropenia, fatigue, back pain, insomnia, asthenia, rash, decreased appetite, cough, pyrexia, muscle spasms, and abdominal pain.
The most frequently reported grade 3 or 4 events in the lenalidomide-plus-dexamethasone arm included neutropenia (27.8%), anemia (18.2%), pneumonia (11.3%), thrombocytopenia (8.3%), asthenia (7.7%), fatigue (7.3%), rash (7.3%), back pain (7%), hypokalemia (6.6%), cataract (5.8%), dyspnea (5.6%), deep-vein thrombosis (5.6%), and hyperglycemia (5.3%). ■