FDA approval of melflufen in combination with dexamethasone for R/R MM

The U.S. Food and Drug Administration (FDA) announced the approval of melphalan flufenamide, also known as melflufen, in combination with dexamethasone for patients with relapsed/refractory multiple myeloma (R/R MM). Patients who were refractory to one proteasome inhibitor, one immunomodulatory agent, one CD38-directed monoclonal antibody, and had been treated with at least four lines of therapy previously are the target group for this treatment. Melflufen is the first peptide-drug conjugate to receive approval from the FDA as an anticancer agent.¹

This approval was based on the results of the phase II HORIZON trial (NCT02963493) in heavily pretreated patients with R/R MM. In total, 157 patients were included in this study, 62% of whom were triple-class refractory and had been treated with at least four lines of therapy previously. In this study, the overall response rate was 29%, with responses lasting for a median of 5.5 months, and the overall survival was 11.6 months. This combination was noted to be active in patients with extramedullary disease (24% achieved a partial response or better), which is a subset known for its aggressive and difficult-to-treat nature.²

Melflufen and dexamethasone were also investigated in the phase I/IIa ANCHOR study (OP-104; NCT03481556) in combination with either daratumumab or bortezomib for the treatment of R/R MM. An overall response rate of 73% and 62% was recorded in the daratumumab and bortezomib cohorts, respectively.

A phase III trial called the OCEAN study (NCT03151811) is currently ongoing to test melflufen and dexamethasone against pomalidomide with dexamethasone.