A Study of Melphalan Flufenamide (Melflufen)-Dex or Pomalidomide-dex for RRMM Patients Refractory to Lenalidomide

Summary

This was a randomized, controlled, open-label, Phase 3 multicenter study which enrolled patients with RRMM following 2-4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy as demonstrated by disease progression on or within 60 days of completion of the last dose of lenalidomide. Patients received either melflufen+dex or pomalidomide+dex.

Timeline

Start

2017-06-12

Primary completion

2021-02-03

Completion

2023-02-03

Outcome

Met primary endpoint

Stopped: “Sponsor assessed all endpoints and collected Overall Survival data for another two years following the primary completion date of 03Feb2021.”

registry analysis (superiority test); Arm A: Melflufen+Dexamethasone vs Arm B: Pomalidomide+Dexamethasone; p = 0.0311; Log Rank NCT03151811 ↗

paper Melflufen plus dexamethasone showed superior progression-free survival than pomalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. PMID 35032434 ↗

Publications

• Acs K, Miettinen JJ, Sergeev P, Heckel T, Diao Y, Witt-Mulder K, Thureson M, Bischler T, Huppunen ME, Suvela M, Obermuller J, Munawar U, Slipicevic A, Bargou RC, Lehmann F, Gelius SS, Norin S, Schjesvold F, Sonneveld P, Stuhmer T, Heckman CA. Efficacy of melflufen in multiple myeloma with mutated or deleted TP53. Exp Hematol Oncol. 2025 Dec 23;14(1):138. doi: 10.1186/s40164-025-00729-1.
• Schjesvold FH, Ludwig H, Delimpasi S, Robak P, Coriu D, Tomczak W, Pour L, Spicka I, Dimopoulos MA, Masszi T, Chernova NG, Sandberg A, Thuresson M, Norin S, Bakker NA, Mateos MV, Richardson PG, Sonneveld P. Health-related quality of life in relapsed/refractory multiple myeloma treated with melflufen and dexamethasone: analyses from the phase III OCEAN study. Haematologica. 2024 Jul 1;109(7):2331-2336. doi: 10.3324/haematol.2023.284635. No abstract available.
• Sonneveld P, Richardson PG, Ludwig H, Dimopoulos MA, Schjesvold FH, Hajek R, Abdulhaq H, Thuresson M, Norin S, Bakker NA, Mateos MV. Benefit Versus Risk Assessment of Melflufen and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Analyses From Longer Follow-up of the OCEAN and HORIZON Studies. Clin Lymphoma Myeloma Leuk. 2023 Sep;23(9):687-696. doi: 10.1016/j.clml.2023.05.004. Epub 2023 May 6.
• Schjesvold FH, Dimopoulos MA, Delimpasi S, Robak P, Coriu D, Legiec W, Pour L, Spicka I, Masszi T, Doronin V, Minarik J, Salogub G, Alekseeva Y, Lazzaro A, Maisnar V, Mikala G, Rosinol L, Liberati AM, Symeonidis A, Moody V, Thuresson M, Byrne C, Harmenberg J, Bakker NA, Hajek R, Mateos MV, Richardson PG, Sonneveld P; OCEAN (OP-103) Investigators. Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomised, head-to-head, open-label, phase 3 study. Lancet Haematol. 2022 Feb;9(2):e98-e110. doi: 10.1016/S2352-3026(21)00381-1. Epub 2022 Jan 12.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Melphalan flufenamide	Peptide	40 mg	Intravenous
Comparator	Pomalidomide	Other / unclassified	4 mg	Oral
Background	Dexamethasone	Small molecule	20 mg	Oral
Background	Dexamethasone	Small molecule	40 mg	Oral

Indications