Year: 2021
Type: article
Abstract: elphalan flufenamide (melflufen) is a peptide-drug conjugate prodrug for melphalan, an alkylating cytotoxic chemotherapy used in the treatment of multiple myeloma.Melflufen recently received accelerated approval from the US Food and Drug Administration (FDA) for the treatment of patients who have received four prior lines of myeloma treatment.The accelerated approval was based on the results of the HORIZON study, which showed an overall response rate of 29% in the intention-to-treat population with a median duration of response (mDoR) of 5.5 months and 24% with a mDoR of 4.2 months in the FDA-approved indication subgroup.Adverse events were mostly haematological values.Although these results appear modest, they are in line with what would be expected in a heavily pretreated patient population, and similar to results for other approved drugs.The confirmatory OCEAN trial (a study of melphalan flufenamide [melflufen]-dex or pomalidomide-dex for RRMM patients refractory to lenalidomide) was reported to have met its primary endpoint of improved progression-free survival compared with pomalidomide.However, on 8 July 2021, the FDA published an alert that the melflufen arm in the OCEAN trial was associated with an increased risk of death, and placed melflufen studies on partial hold.While details are currently unknown, an ongoing subgroup analysis is being performed to determine whether certain patient populations benefit more or less in terms of survival.Several other studies are ongoing, and their results are to be determined.Importantly, after discussion with the FDA, melflufen was withdrawn from the US market based on data from the phase III OCEAN study on 22 October 2021.Based on available published data and our clinical experience, we believe melflufen may be a worthy tool in the myeloma physician's armamentarium but until the earlier mortality signal is resolved, it will not, for the most part, be available in the clinic.
Authors: Dickran Kazandjian, Ola Landgren
Institutions: University of Miami, Sylvester Comprehensive Cancer Center
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4212791034