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Phase 3 DREAMM-8 Trial Reports Progression-Free Survival Benefit With Belantamab Mafodotin Combination in Relapsed or Refractory Multiple Myeloma

In a head-to-head comparison against a bortezomib-based triplet, researchers reported a progression-free survival benefit in patients with at least one previous line of therapy including lenalidomide, though self-reported ocular side-effects were more common with belantamab mafodotin, with minimal overall quality-of-life impact reported in post-hoc analysis.

  • Meletios A Dimopoulos, MD; Meral Beksac, MD; Ludek Pour, MD; Sosana Delimpasi, MD; Vladimir Vorobyev, MD; Hang Quach, MD; et al.

  • November 1, 2025

  • The Lancet Haematology
  • The Lancet Haematology, Volume 12, Issue 11, Pages e876–e886
  • 10.1016/S2352-3026(25)00256-X

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Evidence before this study

The integration of triplet or quadruplet regimens into the first-line treatment setting has significantly improved clinical outcomes in newly diagnosed multiple myeloma, yet patients often relapse, and many have disease that is refractory to treatment. Novel and efficacious therapies with distinct mechanisms of action are urgently needed at first relapse to overcome resistance mechanisms and provide durable responses and improved outcomes. We searched PubMed using the terms “relapsed,” “myeloma,” “BCMA,” and “clinical trial” for studies published from Jan 1, 2000, to Feb 26, 2025. We identified several B-cell maturation antigen (BCMA)-targeting agents that are in clinical development, including chimeric antigen receptor T-cell therapies and bispecific antibodies. However, we found no human studies evaluating BCMA-targeting antibody conjugates other than belantamab mafodotin. Belantamab mafodotin is a BCMA antibody–drug conjugate that showed promising antimyeloma activity and a manageable safety profile as a single agent in heavily pretreated patients with relapsed or refractory multiple myeloma in the first-in-human phase 1 DREAMM-1 (NCT02064387) and phase 2 DREAMM-2 (NCT03525678) trials; following these studies, belantamab mafodotin monotherapy received accelerated approval in the USA. The confirmatory phase 3 DREAMM-3 (NCT04162210) trial showed a numerical progression-free survival benefit with belantamab mafodotin versus pomalidomide plus low-dose dexamethasone, but the benefit was not statistically significant; therefore, GSK withdrew belantamab mafodotin in the USA.

To our knowledge, DREAMM-7 was the first phase 3 head-to-head trial to show improved progression-free survival and overall survival benefit against an anti-CD38-based triplet regimen. Progression-free survival and overall survival were improved with belantamab mafodotin, bortezomib, and dexamethasone compared with daratumumab, bortezomib, and dexamethasone. In the DREAMM-8 trial, belantamab mafodotin, pomalidomide, and dexamethasone (belantamab mafodotin group) was compared with bortezomib, pomalidomide, and dexamethasone (bortezomib group) in patients treated with at least one previous line of therapy, including lenalidomide. The belantamab mafodotin group demonstrated a statistically significant and clinical reduction in the risk of progression or death compared with the bortezomib group; and was associated with a larger proportion of patients achieving complete response or better. The safety profile of belantamab mafodotin was consistent with previous data, with manageable and generally reversible ocular side-effects.

Added value of this study

To our knowledge, DREAMM-8 and DREAMM-7 are among the first phase 3 head-to-head studies demonstrating progression-free survival benefit with a BCMA-targeted antibody-drug conjugate compared with a triplet regimen. Health-related quality of life remained stable over time, and most patients in both treatment groups self-reported minimal severity, interference, and frequency of symptomatic adverse events. Although self-reported ocular side-effects were more common in patients treated with belantamab mafodotin, the negative impact on overall health-related quality-of-life measures was minimal in post-hoc analysis.

Implications of all the available evidence

Belantamab mafodotin, pomalidomide, and dexamethasone is a potential new standard of care in patients with relapsed or refractory multiple myeloma at first relapse based on its statistically significant progression-free survival benefit, clinically meaningful early trend in overall survival, manageable safety profile, and small impact on patients’ quality of life.

Source: The Lancet Haematology

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