Real-World Outcomes of Melflufen Plus Dexamethasone in Heavily Pretreated Relapsed/Refractory Multiple Myeloma After Exposure to Immunotherapies

Autores de IIS La Fe

• David Martínez Campuzano

  Autor

• Clara Sopeña Pell-Ilderton

  Autor

• Mario Arnao Herraiz

  Autor

• 

  Javier De La Rubia Comos

  Autor

Participantes ajenos a IIS La Fe

• Moreno M.J.
• Sánchez M.
• Gascón A.
• Lorente P.
• Montagud M.
• Martí J.P.
• Ríos S.

Grupos

• Hematología y Hemoterapia

Abstract

Introduction: The combination of melphalan fluflenamide (melflufen) and dexamethasone (melf-dex) is approved for patients with relapsed/refractory multiple myeloma (RRMM) after =3 prior lines of therapy; however, the results in patients outside clinical trials, particularly those receiving novel immunotherapies, remain limited. Patients and Methods: We retrospectively collected data from patients with RRMM treated with melf-dex in the real-world setting at 8 Spanish institutions between June 2024 and May 2025. Results: Nineteen patients were included (median age, 64 years; median of 5 prior lines). Soft tissues plasmacytomas were present in 2 patients and high-risk cytogenetics in 7 (4 with 32 high-risk abnormalities). Eighteen patients (95%) and 14 (74%) were triple and penta-class refractory, respectively. Fourteen patients (74%) had prior exposure to anti-BCMA/GPRC5D therapies, including 5 with dual exposure. Response rate was 28% (5/19) in the total cohort and 33% (4/13) in the immunotherapy-exposed subgroup; stable disease rates were 44% and 42%, respectively. Median progression-free survival was 4.8 months (95% CI: 2.5-not reached). At a median follow-up of 5.75 months, median overall survival was not reached. Three patients remained alive and responding beyond nine months. Grade =3 hematologic toxicities were common (thrombocytopenia 68%, neutropenia 68%, anemia 47%). One patient discontinued due to severe thrombocytopenia and bleeding, and one died of sepsis Conclusion: This is the first real-world report of melf-dex after novel immunotherapies, showing efficacy consistent with clinical trials. Melf-dex may be a valuable treatment option in very late relapse, although larger cohorts of patients and longer follow-up are needed. © 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Copyright © 2026 Elsevier Inc. All rights reserved.

Keywords

• Melphalan-flufenamide; Prior immunotherapy; Real-world evidence; Triple and penta-class refractory; =3 lines of therapy