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*, Paul G. Richardson, Heinz Ludwig, Meletios Athanasios Dimopoulos, Fredrik H. Schjesvold, Roman Hájek, Haifaa Abdulhaq, Marcus Thuresson, Stefan Norin, Nicolaas A. Bakker, Maria Victoria Mateos

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)
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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).

Original languageEnglish
Pages (from-to)687-696
Number of pages10
JournalClinical Lymphoma, Myeloma and Leukemia
Volume23
Issue number9
Early online date6 May 2023
DOIs
Publication statusPublished - Sept 2023

Bibliographical note

Funding Information:
The authors would like to thank the patients and their families for participating in this trial and the trial investigators and coordinators for their contributions to the trial. We thank Jared D. Hoffman, MS, PhD, and Katherine Mills-Lujan, PhD, CMPP, of Team 9 Science for providing medical editorial assistance under the guidance of the authors, which was funded by Oncopeptides AB in accordance with Good Publication Practice (GPP) 2022 guidelines.

Publisher Copyright:
© 2023

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