Melphalan Flufenamide Receives Accelerated Approval for Relapsed/Refractory Multiple Myeloma

Melphalan flufenamide, in combination with dexamethasone, has received accelerated approval from the FDA for the treatment of adult patients with relapsed or refractory multiple myeloma (MM) who have received at least four prior lines of therapy and whose disease is triple-class refractory – meaning refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody.

This approval is based on efficacy data from the HORIZON study, in which participants with relapsed/refractory MM received melphalan flufenamide 40 mg intravenously on day one and dexamethasone 40 mg orally (20 mg for patients ≥75 years of age) on days one, eight, 15, and 22 of each 28-day cycle until disease progression or unacceptable toxicity.

Among 97 participants with triple-class refractory disease, the overall response rate was 23.7% and the median duration of response was 4.2 months.

The most common AEs included fatigue, nausea, diarrhea, pyrexia, and respiratory tract infection. The most common laboratory abnormalities, occurring in ≥50% of patients, were increased creatinine and decreased leukocytes, platelets, lymphocytes, neutrophils, and hemoglobin.

Melphalan flufenamide is not indicated or recommended for use as a conditioning regimen for transplant outside of controlled clinical trials. The recommended dosage is 40 mg intravenously over 30 minutes on day one of each 28-day treatment cycle, in combination with dexamethasone.

Sources:, February 26, 2021;, NCT02963493.