Melphalan flufenamide

Melphalan flufenamide, also known as melflufen or J1, is a prodrug of melphalan. Melphalan flufenamide is more readily uptaken by cells than melphalan, and is cleaved to the active metabolite by aminopeptidases. In vitro models show that melphalan is 10 to hundreds of times more potent than melphalan. The increased potency makes melphalan flufenamide a treatment option for patients with relapsed or refractory multiple myeloma who have attempted at least 4 lines of therapy already.

Melphalan flufenamide was granted FDA approval on 26 February 2021.. It has since been withdrawn from the market in the wake of the phase 3 OCEAN trial which showed a decrease in overall survival in comparison to standard treatment with pomalidomide and dexamethasone despite superior progression-free survival.

Melphalan flufenamide is indicated in combination with dexamethasone to treat adults with relapsed or refractory multiple myeloma who have received ≥4 therapies and are refractory to at least one proteasome inhibitor, immunomodulatory agent, and anti-CD38 monoclonal antibody. The FDA has withdrawn the drug from the market for this indication following phase 3 trial data showing decreased overall survival.