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).

Department of Clinical Therapeutics School of Medicine National and Kapodistrian University of Athens Athens Greece

Department of Hemato oncology Faculty of Medicine University of Ostrava Ostrava Czech Republic

Department of Hemato oncology University Hospital Ostrava Ostrava Czech Republic

Department of Hematology Erasmus MC Cancer Institute Rotterdam The Netherlands

Department of Medicine University of California San Francisco Fresno Campus CA

Institute of Cancer Molecular and Cellular Biology and CIBERONC Salamanca Spain

Jerome Lipper Multiple Myeloma Center Dana Farber Cancer Institute Boston MA

KG Jebsen Center for B Cell Malignancies University of Oslo Oslo Norway

Medical Department Center for Oncology Hematology and Palliative Medicine Wilhelminen Cancer Research Institute Vienna Austria

Oncopeptides AB Stockholm Sweden

Oslo Myeloma Center Department of Hematology Oslo University Hospital Oslo Norway

University Hospital of Salamanca Instituto de Investigación Biomédica de Salamanca Salamanca Spain

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$a Sonneveld, Pieter $u Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. Electronic address: p.sonneveld@erasmusmc.nl

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$a Benefit Versus Risk Assessment of Melflufen and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Analyses From Longer Follow-up of the OCEAN and HORIZON Studies / $c P. Sonneveld, PG. Richardson, H. Ludwig, MA. Dimopoulos, FH. Schjesvold, R. Hájek, H. Abdulhaq, M. Thuresson, S. Norin, NA. Bakker, MV. Mateos

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$a 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).

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$a Richardson, Paul G $u Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA

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$a Ludwig, Heinz $u Medical Department Center for Oncology, Hematology and Palliative Medicine, Wilhelminen Cancer Research Institute, Vienna, Austria

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$a Dimopoulos, Meletios-Athanasios $u Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

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$a Hájek, Roman $u Department of Hemato-oncology, University Hospital Ostrava, Ostrava, Czech Republic

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$a Mateos, Maria-Victoria $u University Hospital of Salamanca, Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain; Institute of Cancer Molecular and Cellular Biology and CIBERONC, Salamanca, Spain

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