Dr. Richardson on the FDA Approval of Melphalan Flufenamide in Relapsed/Refractory Multiple Myeloma

Paul G. Richardson, MD, clinical program leader and director of clinical research, Jerome Lipper Multiple Myeloma Center, physician, Dana-Farber Cancer Institute, and RJ Corman Professor of Medicine at Harvard Medical School, discusses the FDA approval of melphalan flufenamide (Pepaxto; melflufen) in relapsed/refractory multiple myeloma.

On February 26, 2021, the FDA granted an accelerated approval to melphalan flufenamide for use in combination with dexamethasone in patients with relapsed/refractory multiple myeloma who have received at least 4 prior lines of therapy and whose disease is refractory to a proteasome inhibitor, an immunomodulatory agent, and a CD38-directed monoclonal antibody.

The regulatory decision was based on findings from the phase 2 HORIZON study, in which the combination induced an overall response rate of 23.7% and a median duration of response of 4.2 months in this heavily pretreated, triple-class refractory patient population.

Melphalan flufenamide is a novel peptide-drug conjugate that targets aminopeptidases and rapidly releases alkylating agents into myeloma cells, explains Richardson. The rationale to evaluate melphalan flufenamide was to improve upon the specificity of melphalan, which is a potent cytotoxic agent in multiple myeloma, Richardson says. In turn, melphalan flufenamide appears to confer low rates of infection and no alopecia. Although myelosuppression was observed with melphalan flufenamide, it was general manageable, concludes Richardson.