Melphalan Flufenamide Is Efficacious and Tolerable in Relapsed/Refractory Myeloma

Melphalan flufenamide was noninferior to pomalidomide in patients with relapsed or refractory myeloma.

Melphalan flufenamide (Pepaxto) has been shown to be noninferior to pomalidomide (Pomalyst) in the treatment of patients with relapsed/refractory multiple myeloma, according to data from the phase 3 OCEAN trial (NCT03151811).1

The hazard ratio (HR) for progression-free survival (PFS), per independent review committee assessment, favored melphalan flufenamide over pomalidomide, at 0.817 (95% CI, 0.659-1.012; P = .0640). The HR for PFS per investigator assessment was 0.790 (95% CI, 0.639-0.976). In both assessments the median PFS for the investigative arm proved to be over 40% higher than for the control arm. Moreover, the overall response rates (ORRs) with melphalan flufenamide and pomalidomide were 32.1% and 26.5%, respectively.

“The efficacy and safety data from the OCEAN study are very encouraging, and the results will be of importance in physicians’ treatment decisions for patients with relapsed and refractory multiple myeloma,” Pieter Sonneveld, MD, PhD, professor of hematology at Erasmus University of Rotterdam and principal investigator of the OCEAN study, stated in a press release. “Melphalan flufenamide has a unique mode of action, which in addition with its tolerability profile, makes the drug on attractive treatment option for many patients.”

In the open-label, global phase 3 trial, investigators set out to examine the safety and efficacy of melflufen flufenamide and dexamethasone vs pomalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma.2 To be eligible for enrollment, patients needed to have previously received 2 to 4 treatments and have been refractory to both lenalidomide (Revlimid) and their last treatment received. If patients previously received pomalidomide, they were excluded.

The primary end point of the trial was progression-free survival (PFS), while key secondary end points include ORR, duration of response (DOR), and overall survival.

Regarding safety, discontinuation rates due to toxicity were noted to be comparable between the melphalan flufenamide and pomalidomide arms. The toxicity profile of melphalan flufenamide also proved to be in line with what has been seen in prior studies; it was also consistent across age subsets.

“The outcome from the phase 3 OCEAN study is very good news for patients with relapsed refractory multiple myeloma,” Klaas Bakker, MD, PhD, executive vice president and chief medical officer at Oncopeptides, added in the release. “This head-to-head comparison was a bold study with an optimal design for demonstrating melphalan flufenamide’s true isolated treatment effects.”

Based on the data, Oncopeptides announced plans to submit a supplementary new drug application to the FDA in Q4 2021. Data from the trial will be presented at an upcoming medical conference.

In February 2021, the FDA approved melphalan flufenamide for use in combination with dexamethasone in adult patients with relapsed or refractory multiple myeloma, who have received at least 4 prior lines of therapy and whose disease is refractory to at least 1 proteasome inhibitor, 1 immunomodulatory agent, and 1 CD38-directed monoclonal antibody. The decision was based on findings from the phase 2 HORIZON trial (NCT02963493), where the doublet elicited an ORR of 23.7% in heavily pretreated patients with relapsed/refractory multiple myeloma, with a median DOR of 4.2 months.3

Moreover, the ongoing phase 3 LIGHTHOUSE trial (NCT04649060) is examining the safety and efficacy of melphalan flufenamide plus daratumumab (Darzalex) vs daratumumab alone in patients with relapsed/refractory multiple myeloma.


  1. Phase 3 OCEAN study demonstrates that melphalan flufenamide is at least as efficacious as pomalidomide, the most used medicine in relapsed refractory multiple myeloma. News release. Oncopeptides Inc. May 26, 2021. Accessed May 26, 2021.
  2. Schjesvold F, Robak P, Pour L, et al. OCEAN: a randomized phase III study of melflufen + dexamethasone to treat relapsed refractory multiple myeloma. Future Oncol. 2020;16(11):631-641. doi:10.2217/fon-2020-0024
  3. FDA approves Oncopeptides' PEPAXTO (melphalan flufenamide) for patients with relapsed or refractory multiple myeloma. News release. Oncopeptides AB (publ). February 26, 2021. Accessed May 26, 2021.

This article was originally posted on OncLive as, "Melphalan Flufenamide Noninferior to Pomalidomide in Relapsed/Refractory Myeloma."