FDA Grants Expanded Indication for Lenalidomide in Treatment of Multiple Myeloma

The FDA yesterday expanded the indication for lenalidomide (Revlimid) to include patients with multiple myeloma (MM) as maintenance therapy following autologous hematopoietic stem cell transplant (auto-HSCT).

Revlimid is the first and only treatment to receive FDA approval for maintenance following auto-HSCT, according to a press release.

“Autologous stem cell transplant (ASCT) after induction therapy is part of the continuum of care for transplant-eligible multiple myeloma patients,” said Philip McCarthy, MD, director or the Blood and Marrow Transplant Center, Department of Medicine at Roswell Park Cancer Institute. “However, most patients will still see their disease recur or progress after this treatment. 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 approval was based on 2 large studies that compared 10-mg capsules of lenalidomide maintenance therapy administered until disease progression or unacceptable toxicity after auto-HSCT compared with no maintenance.

The studies CALGB 100104 and IFM 2005-02 together included more than 1000 patients. Furthermore, the primary efficacy endpoint in both studies was progression-free survival (PFS), as defined from randomization to the date of progression or death, whichever occurred first.

The randomized, controlled, double-blind, multi-center, phase 3 CALGB 100104 study was conducted in 47 centers. There were 460 patients aged 18 to 70 years who were newly diagnosed with MM, had undergone induction therapy within 12 months of diagnosis and achieved at least stable disease (SD) or better 90 to 100 days following ASCT.

The participants were randomized to receive either lenalidomide maintenance or placebo. The maintenance group received 10-mg dose per day—–which was increased to 15 mg per day after 3 months if well-tolerated––until disease progression, intolerable adverse events (AEs), patient withdrawal, or death. Approximately 58% of patients had their dosage increased to 15 mg per day.

The results of the CALGB 100104 of lenalidomide study showed a median PFS of 5.7 years compared with 1.9 years for no maintenance.

In the double-blind, multi-center, controlled phase 3 IFM 2005-02 study at 78 centers in Belgium, France, and Switzerland included 614 newly diagnosed patients with MM who were younger than 65 years, had undergone induction therapy, and did not present signs of disease progression within 6 months of undergoing ASCT.

The participants were randomized to receive a 2-month consolidation regimen of lenalidomide monotherapy 25 mg per day on days 21 and 28, followed by either lenalidomide maintenance or placebo. The lenalidomide dose was 10 mg per day until disease progression, intolerable AEs, patient withdrawal, or death. After 3 months if the drug was well tolerated the dose was increased to 15 mg per day. A dose increase occurred in 60% of patients.

The results of IFM 2005-02 showed a benefit with a median PFS of 3.9 years compared with 2 years for no maintenance. Individual studies were not powered for an overall survival endpoint, according to the release.

In a descriptive analysis, the median overall survival (OS) in the CALGB 100104 study was 9.3 years for patients administered lenalidomide compared with 7 years for no maintenance. In the IFM 2005-02 study, the median OS was 8.8 years with lenalidomide compared with 7.3 years with no maintenance.

The most common AEs in the lenalidomide arm across both maintenance studies were neutropenia, thrombocytopenia, leukopenia, anemia, upper respiratory tract infection, bronchitis, nasopharyngitis, cough, gastroenteritis, diarrhea, rash, fatigue, asthenia, muscle spasm, and pyrexia.

The most frequent grade 3 or 4 reactions were neutropenia, thrombocytopenia, and leukopenia, according to the press release. Onset of AEs were generally highest in the first 6 months of treatment with lenalidomide, and then the frequencies decreased over time or remained stable throughout treatment.

“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 of Global Hematology and Oncology for Celgene. “By expanding the approval for [lenalidomide] to include post-transplant maintenance, patients have the potential to maintain those responses, and, importantly, delay progression of the disease.”