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FDA Grants Accelerated Approval to Melphalan Flufenamide for Relapsed or Refractory Multiple Myeloma


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On February 26, the U.S. Food and Drug Administration (FDA) granted accelerated approval to melphalan flufenamide (Pepaxto) in combination with dexamethasone for adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody.

HORIZON Trial

Efficacy was evaluated in HORIZON (ClinicalTrials.gov identifier NCT02963493), a multicenter, single-arm trial. Eligible patients were required to have relapsed refractory multiple myeloma. Patients received melphalan flufenamide at 40 mg intravenously on day 1 and dexamethasone at 40 mg orally (20 mg for patients ≥ 75 years old) on days 1, 8, 15, and 22 of each 28-day cycle until disease progression or unacceptable toxicity.

Efficacy was evaluated in a subpopulation of 97 patients who had received four or more lines of prior therapy and were refractory to at least one proteasome inhibitor, one immunomodulatory agent, and a CD38-directed antibody. The main efficacy outcome measure was overall response rate and duration of response assessed by investigators according to the International Myeloma Working Group criteria. The overall response rate was 23.7% (95% confidence interval [CI] = 15.7%–3.4%) and median duration of response was 4.2 months (95% CI = 3.2–7.6 months).

Safety was evaluated in the 157 patients enrolled in HORIZON. The most common adverse reactions (> 20%) were fatigue, nausea, diarrhea, pyrexia, and respiratory tract infection. The most common laboratory abnormalities (≥ 50%) were decreased leukocytes, platelets, lymphocytes, neutrophils, and hemoglobin, and increased creatinine. The safety and efficacy of melphalan flufenamide has not been established for use as a conditioning regimen in patients receiving transplant.

More About Melphalan Flufenamide

The recommended dose of melphalan flufenamide is 40 mg intravenously over 30 minutes on day 1 of each 28-day treatment cycle, in combination with dexamethasone. For full prescribing information, visit fda.gov.

This indication was approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

This application was granted Priority Review and Orphan Drug designation.


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