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. 2023 Sep;23(9):687-696.
doi: 10.1016/j.clml.2023.05.004. Epub 2023 May 6.

Benefit Versus Risk Assessment of Melflufen and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Analyses From Longer Follow-up of the OCEAN and HORIZON Studies

Pieter Sonneveld  1 , Paul G Richardson  2 , Heinz Ludwig  3 , Meletios-Athanasios Dimopoulos  4 , Fredrik H Schjesvold  5 , Roman Hájek  6 , Haifaa Abdulhaq  7 , Marcus Thuresson  8 , Stefan Norin  8 , Nicolaas A Bakker  8 , Maria-Victoria Mateos  9
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Free article

Benefit Versus Risk Assessment of Melflufen and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Analyses From Longer Follow-up of the OCEAN and HORIZON Studies

Pieter Sonneveld et al. Clin Lymphoma Myeloma Leuk. 2023 Sep.
Free article

Abstract

Introduction: Melphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone demonstrated superior progression-free survival (PFS) but directionally different overall survival (OS) favoring pomalidomide (hazard ratio [HR], 1.10) in OCEAN.

Methods: These analyses further investigated prognostic subgroups impacting survival in updated data from the randomized, phase 3 OCEAN study (NCT03151811; date: February 3, 2022) and the phase 2 HORIZON study (NCT02963493; date: February 2, 2022).

Results: In OCEAN, subgroups prognostic for OS were age (P = .011; <65 years favored pomalidomide) and no previous autologous stem cell transplant (ASCT) or progression >36 months after ASCT (P = .001; favored melflufen). Overall, 245 of 495 (49%) patients randomized had received a previous ASCT, of which 202 (82%) had progressed within 36 months following their ASCT. When excluding patients who had progressed <36 months post-ASCT (melflufen group, n = 145; pomalidomide group, n = 148), median OS was 23.6 months with melflufen and 19.8 months with pomalidomide (HR, 0.83 [95% CI, 0.62-1.12]; P = .22). Among patients with triple-class refractory disease in HORIZON, patients who had progressed <36 months post-ASCT (n = 58) had a lower response rate and shorter duration of response and PFS than the remaining patients (n = 52). Safety was consistent with previous reports.

Conclusion: These analyses demonstrate a consistent benefit for melflufen and dexamethasone in patients with relapsed/refractory multiple myeloma who have not received an ASCT or progressed >36 months after receiving an ASCT (ClinicalTrials.gov identifier: NCT03151811).

Keywords: Autologous stem cell transplant; Melphalan flufenamide; efficacy; multiple myeloma; pomalidomide; safety.

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Conflict of interest statement

Disclosure Funding was provided by Oncopeptides AB. P.S. has received payment or honoraria and research funding from Amgen, Celgene, Janssen, Karyopharm, and Takeda and payment or honoraria from Bristol Myers Squibb. P.G.R. has received consulting fees from AstraZeneca, Bristol Myers Squibb/Celgene, GlaxoSmithKline, Janssen, Karyopharm, Protocol Intelligence, Regeneron, Sanofi, Secura Bio, and Takeda and grants or contracts from Bristol Myers Squibb/Celgene, Karyopharm, Oncopeptides, and Takeda. H.L. has received grants or contracts from Amgen, Sanofi, and Takeda; consulting fees from Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen-Cilag, Pfizer, Sanofi, and Takeda; payment or honoraria from Amgen, Bristol Myers Squibb, Celgene, Janssen-Cilag, Pfizer, Sanofi, and Takeda; and has participated on a data safety monitoring board or advisory board for Amgen, Bristol Myers Squibb, Celgene, Sanofi, and Takeda. M.-A.D. has received payment or honoraria for participation on an advisory board for Amgen, BeiGene, Bristol Myers Squibb, Janssen, and Takeda. F.H.S. has received grants or contracts from Celgene, GlaxoSmithKline, Janssen, Oncopeptides, Targovax, and Sanofi; payment or honoraria from AbbVie, Amgen, Bristol Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Janssen, Novartis, Oncopeptides, Pfizer, Sanofi, SkyliteDX, and Takeda; and participated on a data safety monitoring board or advisory board for AbbVie, Celgene, GlaxoSmithKline, Janssen, Oncopeptides, Sanofi, and Takeda. R.H. has received grants or contracts from Novartis and Takeda; consulting fees and payment or honoraria from AbbVie, Amgen, Bristol Myers Squibb, Janssen, PharmaMAR, and Takeda; consulting fees from Novartis; support for attending meetings and/or travel from Takeda; and has participated on a data safety monitoring board or advisory board for Amgen and Takeda. H.A. has received payment or honoraria from Amgen, Alexion, and Oncopeptides and has participated on a data safety monitoring board or advisory board for Amgen, Bristol Myers Squibb, Genentech, Janssen, MorphoSys and Novartis. M.T. is a consultant of and receives stock or stock options from Oncopeptides. S.N. is an employee of, has participated on a data safety monitoring board or advisory board for, and receives stock or stock options from Oncopeptides. N.A.B. is an employee of and receives stock or stock options from Oncopeptides. M.-V.M. has received payment or honoraria for lectures, presentations, speakers’ bureau, manuscript writing, or education events from Amgen, Bristol Myers Squibb/Celgene, GlaxoSmithKline, Janssen, Pfizer, Sanofi, and Takeda; and has participated on a data safety monitoring board or advisory board for Amgen, Bristol Myers Squibb/Celgene, GlaxoSmithKline, Janssen, Oncopeptides, Pfizer, Sanofi, and Takeda.

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