FDA Approves Maintenance Lenalidomide for Myeloma

The FDA has approved lenalidomide (Revlimid) as a maintenance therapy for patients with multiple myeloma following autologous hematopoietic stem cell transplant (auto-HSCT), according to Celgene, the manufacturer of the treatment.

The data for the approval came from 2 large trials (1000+ patients each) that compared maintenance lenalidomide versus no maintenance after auto-HSCT. The primary endpoint of both studies was progression-free survival (PFS).

In CALGB 100104, the median PFS was 5.7 years (95% CI, 4.4-not estimable) with lenalidomide maintenance versus 1.9 years (95% CI,1.6-2.5) for no maintenance, representing a 3.8-year benefit (HR, 0.38; 95% CI, 0.28-0.50). In the IFM 2005-02 trial, the median PFS was 3.9 years (95% CI, 3.3-4.7) versus 2 years (95% CI, 1.8-2.3), respectively, representing a 1.9-year benefit (HR, 0.53; 95% CI, 0.44-0.64).

The median overall survival (OS) in CALGB 100104 was 9.3 years (95% CI, 8.5-not estimable) with lenalidomide maintenance versus 7 years (95% CI, 5.9-8.6) for no maintenance (HR 0.59; 95% CI, 0.44-0.78). In the IFM 2005-02 trial, the median OS was 8.8 years (95% CI, 7.4-not estimable) versus 7.3 years (95% CI, 6.7-9.0), respectively (HR, 0.90; 95% CI, 0.72-1.13).

"Autologous stem cell transplant after induction therapy is part of the continuum of care for transplant-eligible multiple myeloma patients. However, most patients will still see their disease recur or progress after this treatment," Philip McCarthy, MD, director, Blood and Marrow Transplant Center, Department of Medicine at Roswell Park Cancer Institute, said in a statement.

"Lenalidomide maintenance therapy, which has been shown to increase progression-free survival following autologous stem cell transplant in clinical trials can be considered a standard of care for these patients," added McCarthy.

The doubled-blind phase III CALGB 100104 trial randomized patients with multiple myeloma to maintenance lenalidomide or placebo after first-line chemotherapy and ASCT. Lenalidomide was started at 10 mg daily and elevated to 15 mg daily at 3 months for patients who tolerated the initial treatment. The trial was conducted at 47 locations in the United States. The primary endpoint was time to tumor progression.

IFM 2005-02 was a phase III double-blind trial in which treatment-naïve patients with multiple myeloma who had received induction chemotherapy and ASCT were randomized in a 1:1 ratio to consolidation lenalidomide (25 mg/day on days 1-21 of each 28-day cycle, for 2 cycles) followed by placebo or maintenance lenalidomide (10 mg/day induction dose increased to 15 mg/day at 3 months if tolerated). The study was conducted at 78 centers in France, Belgium, and Switzerland, and had a primary endpoint of posttransplant progression-free survival.

The most common all-grade adverse events (AEs) across the the 2 trials (CALGB 100104, IFM 2005-02, respectively) were neutropenia (79%, 61%), thrombocytopenia (72%, 24%), leukopenia (23%, 32%), anemia (21%, 9%), upper respiratory tract infection (27%, 11%), bronchitis (5%, 47%), nasopharyngitis (2%, 35%), cough (10%, 27%), gastroenteritis (0%, 23%), diarrhea (55%, 39%), rash (32%, 8%), fatigue (23%, 11%), asthenia (0%, 30%), muscle spasm (0%, 33%), and pyrexia (8%, 21%). The most common grade 3/4 AEs across both trials included neutropenia, thrombocytopenia, and leukopenia.

A meta-analysis of data pooled from CALGB 100104, IFM 2005-02, and a third randomized phase III trial, GIMEMA-RVMM-PI-209, was presented at the 2016 ASCO Annual Meeting. The findings showed that maintenance lenalidomide following frontline treatment with high-dose melphalan and ASCT reduced the risk of death by 26% versus placebo or no maintenance in patients with multiple myeloma. The 7-year overall survival (OS) rate was 62% with maintenance lenalidomide versus 50% in patients who did not receive the therapy.

"In newly-diagnosed multiple myeloma, auto-HSCT remains a viable option for many patients and often provides a strong response against the disease," Michael Pehl, president, Global Hematology and Oncology for Celgene, said in a statement. "By expanding the approval for Revlimid to include post-transplant maintenance, patients have the potential to maintain those responses and, importantly, delay progression of the disease."