Posted: Monday, September 26, 2022
The Oncologic Drugs Advisory Committee (ODAC) of the U.S. Food and Drug Administration (FDA) recently voted 14 to 2 that the risk-benefit profile of the alkylating agent melphalan flufenamide (Pepaxto) is not favorable for the currently indicated population of patients with relapsed or refractory multiple myeloma. The concerns behind the regulatory agency’s position included the potential detriment in overall survival, failure to show an improvement in progression-free survival, and lack of an appropriate dose.
In early 2021, the FDA granted accelerated approval to melphalan flufenamide in combination with dexamethasone for the treatment of adults with relapsed or refractory multiple myeloma. Eligible patients had received at least four prior lines of therapy and their disease was refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody. This approval was based on the results of the phase II HORIZON trial (ClinicalTrials.gov identifier NCT02963493). However, the confirmatory phase III OCEAN trial (NCT03151811) demonstrated an increased risk of death associated with the regimen versus the control arm.