FDA Approves Lenalidomide as Maintenance Therapy for Patients With Multiple Myeloma Following Autologous Stem Cell Transplant

Key Points

  • The FDA has expanded the indication for lenalidomide to include use as maintenance therapy for patients with multiple myeloma following autologous stem cell transplant.
  • Approval was based on two randomized, controlled trials (CALGB 100104 and IFM 2005-02) that demonstrated a progression-free survival benefit of 3.8 years and 1.9 years, respectively, with maintenance lenalidomide after autologous stem cell transplant.
  • Median overall survival in CALGB 100104 was 9.3 years for patients who received lenalidomide vs 7 years for no maintenance. In IFM 2005-02, median overall survival was 8.8 years for patients who received lenalidomide vs 7.3 years for no maintenance.

On February 22, the U.S. Food and Drug Administration (FDA) expanded the existing indication for lenalidomide (Revlimid) 10 mg capsules to include use for patients with multiple myeloma as maintenance therapy following autologous hematopoietic stem cell transplant. The expanded indication makes lenalidomide the first and only treatment to receive FDA approval for maintenance use following autologous hematopoietic stem cell transplant.

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

Clinical Trial Findings

The approval was based on two large studies—CALGB 100104 and IFM 2005-02—including more than 1,000 patients comparing lenalidomide maintenance therapy given until disease progression or unacceptable toxicity after autologous hematopoietic stem cell transplant vs no maintenance. In both studies, the primary efficacy endpoint was progression-free survival.

In the most current progression-free survival analysis, Study 1 (CALGB 100104) demonstrated a median progression-free survival of 5.7 years (95% confidence interval [CI] = 4.4–not estimable) vs 1.9 years (95% CI = 1.6–2.5) for no maintenance, a difference of 3.8 years (hazard ratio [HR] = 0.38; 95% CI = 0.28–0.50).

Study 2 (IFM 2005-02) also showed a benefit with a median progression-free survival of 3.9 years (95% CI = 3.3–4.7) vs 2 years (95% CI =1.8­–2.3) for no maintenance, a difference of 1.9 years (HR = 0.53; 95% CI = 0.44–0.64).

Individual studies were not powered for an overall survival endpoint.

A descriptive analysis showed the median overall survival in Study 1 was 9.3 years (95% CI = 8.5–not estimable) for patients who received lenalidomide vs 7 years (95% CI = 5.9–8.6) for no maintenance (HR = 0.59; 95% CI = 0.4­–0.78). In Study 2, median overall survival was 8.8 years (95% CI = 7.4–not estimable) for patients who received lenalidomide vs 7.3 years (95% CI = 6.7–9.0) for no maintenance (HR = 0.90; 95% CI = 0.72–1.13).

Adverse Events

The most frequently reported adverse reactions in ≥ 20% (lenalidomide arm) across both maintenance studies (Study 1, Study 2 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 frequently reported Grade 3 or 4 reactions (more than 20% in the lenalidomide arm) included neutropenia, thrombocytopenia, and leukopenia.

The frequencies of onset of adverse reactions were generally highest in the first 6 months of treatment and then the frequencies decreased over time or remained stable throughout treatment.

In patients receiving lenalidomide maintenance therapy, hematologic second primary malignancies occurred in 7.5% of patients compared to 3.3% in patients receiving placebo. The incidence of hematologic plus solid tumor (excluding squamous cell carcinoma and basal cell carcinoma) second primary malignancies was 14.9%, compared to 8.8% in patients receiving placebo with a median follow-up of 91.5 months. Nonmelanoma skin cancer second primary malignancies, including squamous cell carcinoma and basal cell carcinoma, occurred in 3.9% of patients receiving lenalidomide maintenance, compared to 2.6% in the placebo arm.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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