The U.S. Food and Drug Administration (FDA) expanded the approval of lenalidomide to include maintenance therapy for patients with multiple myeloma (MM) who have received autologous hematopoietic cell transplantation (AHCT).
The approval was based on the results of two studies that compared lenalidomide maintenance therapy versus no maintenance in more than 1,000 patients.
The double-blind, randomized, phase III CALGB 100104 study was conducted at 47 U.S. centers and randomized patients to receive maintenance lenalidomide (started at 10 mg daily and elevated to 15 mg daily at three months if tolerated) or placebo after firstline chemotherapy and AHCT. The median progression-free survival (PFS; primary endpoint) was 5.7 years among those who received lenalidomide maintenance therapy, compared with 1.9 years for those who did not (hazard ratio [HR] = 0.38; 95% CI 0.28-0.5). Overall survival (OS) was also significantly improved in those treated with lenalidomide therapy, with a median of 9.3 years versus 7.0 years (HR=0.59; 95% CI 0.44-0.78).
The double-blind, phase III IFM 2005-02 study was conducted at 78 centers in Belgium, France, and Switzerland and included treatment-naïve patients who had previously received induction chemotherapy and AHCT. They were randomized 1:1 to receive consolidation lenalidomide (25 mg/day on days 1-21 of each 28-day cycle for two cycles) followed by placebo or maintenance lenalidomide (10 mg/day induction dose increased to 15 mg/day at three months if tolerated). The median PFS (primary endpoint) was 3.9 years among those who received lenalidomide maintenance therapy, compared with 2.0 years for those who did not (HR=0.53; 95% CI 0.44-0.64). The OS benefit with lenalidomide maintenance therapy was slightly better, but not significantly so: 8.8 years versus 7.3 years (HR=0.90; 95% CI 0.72-1.13).
The most common adverse events (AEs) associated with lenalidomide maintenance therapy in the first and second studies included neutropenia (79% and 61%), thrombocytopenia (72% and 24%), leukopenia (23% and 32%), anemia (21% and 9%), upper respiratory tract infection (27% and 11%), bronchitis (5% and 47%), nasopharyngitis (2% and 35%), cough (10% and 27%), gastroenteritis (0% and 23%), diarrhea (55% and 39%), rash (32% and 8%), and fatigue (23% and 11%). The most common grade 3/4 AEs were neutropenia, thrombocytopenia, and leukopenia.
Hematologic secondary primary malignancies occurred in 7.5 percent of patients who received lenalidomide maintenance therapy and 3.3 percent of patients who did not (p value not reported).
Source: U.S. Food and Drug Administration press release, February 22, 2017.