Maintenance Revlimid Gains FDA Approval for Multiple Myeloma

Revlimid (lenalidomide) was granted approval by the Food and Drug Administration (FDA) as a maintenance therapy for patients with multiple myeloma who have had autologous hematopoietic stem cell transplant (auto-HSCT), according to Celgene, the manufacturer of the treatment.

The data for the approval came from two large trials (1000+ patients each) that compared maintenance Revlimid 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 with Revlimid maintenance versus 1.9 years for no maintenance, representing a 3.8-year benefit. In the IFM 2005-02 trial, the median PFS was 3.9 years versus two years, respectively, representing a 1.9-year benefit.

The median overall survival (OS) in CALGB 100104 was 9.3 years with Revlimid maintenance versus seven years for no maintenance. In the IFM 2005-02 trial, the median OS was 8.8 years versus 7.3 years, respectively.

"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, M.D., 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 3 CALGB 100104 trial randomized patients with multiple myeloma to maintenance Revlimid or placebo after first-line chemotherapy and ASCT. Revlimid was started at 10 mg daily and elevated to 15 mg daily at three 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 3 double-blind trial in which treatment-naïve patients with multiple myeloma who had received induction chemotherapy and ASCT were randomized in a 1 to 1 ratio to consolidation Revlimid (25 mg/day on days one to 21 of each 28-day cycle, for two cycles) followed by placebo or maintenance Revlimid (10 mg/day induction dose increased to 15 mg/day at three 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 two trials (CALGB 100104, IFM 2005-02, respectively) were neutropenia (79 percent, 61 percent), thrombocytopenia (72 percent, 24 percent), leukopenia (23 percent, 32 percent), anemia (21 percent, 9 percent), upper respiratory tract infection (27 percent, 11 percent), bronchitis (5 percent, 47 percent), nasopharyngitis (2 percent, 35 percent), cough (10 percent, 27 percent), gastroenteritis (0 percent, 23 percent), diarrhea (55 percent, 39 percent), rash (32 percent, 8 percent), fatigue (23 percent, 11 percent), asthenia (0 percent, 30 percent), muscle spasm (0 percent, 33 percent) and pyrexia (8 percent, 21 percent). The most common grade 3/4 AEs across both trials included neutropenia, thrombocytopenia and leukopenia.

"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.”