Priority Review of melflufen for patients with triple-class refractory MM by FDA

The first-in-class peptide–drug conjugate melphalan flufenamide, also known as melflufen (MF), in combination with dexamethasone is to receive priority review by the U.S. Food and Drug Administration (FDA) on February 28, 2021.¹ MF in combination with dexamethasone is intended to treat adult patients with triple-class refractory multiple myeloma (MM), i.e., patients with disease refractory to one immunomodulatory agent, one proteasome inhibitor, and one anti-CD38 monoclonal antibody.

The New Drug Application was made following the results of the HORIZON phase II trial (NCT02963493) which investigated the efficacy and safety of intravenous MF with dexamethasone in patients with relapsed/refractory MM. MF exhibited an overall response rate of 26% in the group of patients who were triple-class refractory and showed a manageable safety profile. In the ongoing phase III trial OCEAN (NCT03151811), MF plus dexamethasone is being compared with pomalidomide plus dexamethasone in patients with MM treated with 2–4 prior lines of therapy and refractory to lenalidomide.^2,3

MF is readily taken up by myeloma cells due to its lipophilic nature and, once inside the cell, is hydrolyzed by peptidases. This causes the release of alkylating agents in the tumor cell. The mode of action of MF takes advantage of the fact that aminopeptidases are overexpressed in tumor cells, especially in advanced disease.¹