The U.S. Food and Drug Administration has approved the anti-CD20 therapy Revlimid (lenalidomide) as a maintenance therapy for multiple myeloma patients who received an autologous hematopoietic stem cell transplant (auto-HSCT).
Revlimid, which extended the time to disease progression and survival in years compared to placebo, is now the only FDA-approved medicine for maintenance use following auto-HSCT.
“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 press release. “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.”
The FDA’s decision was based on data from two Phase 3 clinical trials that together included more than 1,000 myeloma patients who received auto-HSCT.
The Phase 3 CALGB 100104 (NCT00114101) is a randomized, placebo-controlled, double-blind, multi-center study designed to assess the safety and effectiveness of Revlimid versus placebo in 460 newly diagnosed myeloma patients, aged between 18 and 70 years. Eligible participants had received induction therapy within 12 months of diagnosis, and had achieved at least stable disease 90-100 days following auto-HSCT.
Patients were randomized to receive either placebo or Revlimid, starting at a 10 mg/day dosing and increasing to 15 mg/day after three months, if tolerated. Treatment was administered until disease progression, unacceptable toxicity, withdrawal, or death.
Results revealed a median progression-free survival of 5.7 years in the Revlimid group versus 1.9 years in the no-maintenance group, a difference of 3.8 years. Median overall survival in each group was 9.3 years and 7 years, respectively.
The Phase 3 IFM 2005-02 trial (NCT00430365) is a controlled, double-blind, multi-center study, conducted by the University Hospital of Toulouse at 78 centers in France, Belgium and Switzerland. The study was designed to assess the safety and efficacy of a two-month Revlimid consolidation mono-therapy followed by either Revlimid or placebo in 614 newly diagnosed myeloma patients.
Eligible patients were younger than 65 years, had received induction therapy before auto-HSCT, and did not have any signs of disease progression within six months of the transplant.
Participants then were randomized to receive a consolidation regimen of Revlimid mono-therapy (25 mg/day in the first 21 days of 28-day cycles), followed by either Revlimid maintenance, starting at a 10 mg/day dosing and increasing to 15 mg/day after three months, or placebo, until disease progression or unacceptable toxicity.
Data from this trial revealed a median progression-free survival of 3.9 years in the Revlimid group versus 2 years in the placebo group – a difference of 1.9 years. Median overall survival was 8.8 years and 7.3 years in the treatment and control arm, respectively.
“In newly-diagnosed multiple myeloma, auto-HSCT remains a viable option for many patients and often provides a strong response against the disease,” said Michael Pehl, president, Global Hematology and Oncology for Celgene. “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.”