OCEAN (OP-103): Melflufen/Dexamethasone Compared with Pomalidomide/Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma-Age Subgroup Analysis of Older Patients

Background: Older patients (pts) with relapsed/refractory multiple myeloma (RRMM) represent a particularly difficult-to-treat population due to comorbidities, frailty or reduced fitness level, and treatment with concomitant medications (Larocca et al. Leukemia. 2018;32:1697); further, pts may have limited therapeutic options due to ineligibility to receive more intensive treatments (eg, autologous stem cell transplant [ASCT]). Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and thereby rapidly releases alkylating agents into tumor cells. Melflufen + dexamethasone (dex) showed clinically meaningful efficacy and a manageable safety profile in pts with heavily pretreated RRMM in the phase 2 HORIZON study (OP-106; NCT02963493; Richardson et al. J Clin Oncol. 2021;39:757), which led to its accelerated approval in the United States. In the phase 3 OCEAN study (OP-103; NCT03151811; Oncopeptides. Press release. July 8, 2021), a head-to-head comparison of melflufen + dex and pomalidomide (pom) + dex showed superiority of melflufen (vs pom) with a 39% longer median progression-free survival (PFS) (HR, 0.79 [95% CI, 0.64-0.98], P=0.0311), but no clear overall survival (OS) benefit. This analysis compares the efficacy between pts in the melflufen arm vs pom arm based on age and prior ASCT in the OCEAN study.