FDA Approves Belantamab Mafodotin Combo for Relapsed or Refractory Multiple Myeloma

Following an extended review period, the FDA approved belantamab mafodotin (Blenrep; GSK) in combination with bortezomib and dexamethasone (BVd) for patients with relapsed or refractory multiple myeloma following at least 2 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, according to a press release from GSK.1 

The approval is based on data from the phase 3 DREAMM-7 (NCT04246047) randomized clinical trial, which showed statistically significant and clinically meaningful progression-free survival (PFS) results for the combination regimen vs standard triplet therapy. DREAMM-7 also demonstrated improved overall survival (OS) with belantamab mafodotin vs daratumumab-based triplet therapy.

Belantamab mafodotin has potential to fill a gap in the community setting, where many patients with multiple myeloma receive care.| Image credit: wladimir1804 - stock.adobe.com

Belantamab mafodotin, an antibody-drug conjugate (ADC) targeting B-cell maturation antigen (BCMA), joins a growing number of therapies in the dynamic multiple myeloma treatment space in recent years, including BCMA-directed chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies. However, belantamab mafodotin has the potential to fill a gap in the community setting, where many patients with multiple myeloma receive care.

“An important point here is that both BCMA-directed CAR T cells and bispecifics are not readily available out in the community,” Hearn Jay Cho, MD, PhD, chief medical officer at the Multiple Myeloma Research Foundation, told The American Journal of Managed Care® in an interview. “…[belantamab mafodotin], in that setting, is an effective BCMA-directed agent that can be delivered out in the community. There's no cytokine release syndrome risk, it does not require hospitalization, and it can be delivered in an office or infusion center. I foresee that there's going to be a fairly sizable portion of the myeloma community that gets their care out in community medical centers and community practices that are going to need access to something like [belantamab mafodotin].”

DREAMM-7 randomized 494 patients to receive either BVd or daratumumab with bortezomib plus dexamethasone (DVd) following at least 1 prior line of multiple myeloma therapy, and DREAMM-8 randomized 302 patients to receive either BPd or bortezomib and pomalidomide plus dexamethasone (PVd) after at least 1 prior line of multiple myeloma therapy, including a lenalidomide-containing regimen.

In DREAMM-7, the median PFS was 36.6 months in the BVd cohort vs 13.4 in the DVd cohort (HR, 0.41; 95% CI, 0.31-0.53; P < .001).2 At a median follow-up of 39.4 months, there was also a statistically significant, clinically meaningful 42% reduction in the risk of death with BVd vs DVd (HR, 0.58; 95% CI, 0.43-0.79; P = .00023).3 The OS rate at 3 years was 74% in the BVd arm vs 60% in the DVd arm.

Notably, ocular adverse events were much more common among patients receiving belantamab mafodotin combinations vs standard care, and cytopenias were another notable AE. However, the efficacy data are strong, and dosing adjustments may hold potential to reduce the risk of AEs, Cho explained.

“I would emphasize that this is against the backdrop of the efficacy data,” Cho said. “[Belantamab mafodotin] as a single agent and in combinations is effective—there's no question. Both the response rate data and the progression-free survival data were quite favorable. However, the toxicity data were also of great concern. In the risk–benefit equation of any given therapy, what's the potential for benefit? What are the potential risks? This makes it somewhat less favorable for [belantamab mafodotin], so it's important to understand: since we know that the agent is effective, can we give it in a way that is less toxic? And I think there's a lot of interest in understanding whether the dosing interval makes a difference.”

Belantamab mafodotin is also being investigated in combination with pomalidomide plus dexamethasone (BPd) vs bortezomib and pomalidomide plus dexamethasone (PVd) in the DREAMM-8 (NCT04484623) randomized clinical trial, which has also shown statistically significant and clinically meaningful PFS results.3 At 21.8 months of follow-up, DREAMM-8 showed a 12-month estimated progression-free survival of 71% (95% CI, 63-78) with BPd vs 51% (95% CI, 42-60) with PVd (HR, 0.52; 95% CI, 0.37-0.73; P < .001). Longer follow-up showed a persistent clinically meaningful PFS benefit with BPd vs PVd (32.6 months vs 12.5 months, respectively [HR, 0.49; 95% CI, 0.35-0.68]).

The FDA approval of belantamab mafodotin adds to regulatory approvals in the United Kingdom, Japan, Canada, Switzerland (DREAMM-8 regimen), and the United Arab Emirates.1

"Today’s FDA approval of [belantamab mafodotin] is another significant milestone, providing potential for superior efficacy, including overall survival, to US patients," Tony Wood, chief scientific officer, GSK, said in a press release.1 "There is an urgent need for new and novel therapies, as nearly all patients with multiple myeloma experience relapse and re-treating with the same mechanism of action often leads to suboptimal outcomes. As the only anti-BCMA agent that can be administered across health care settings, including in community centers where 70% of patients receive care, [belantamab mafodotin] fulfills a major patient need. We believe [belantamab mafodotin] can redefine treatment for patients with multiple myeloma in all parts of the world, and we are accelerating its development in earlier lines of therapy to support its use across all stages of this difficult-to-treat cancer.” 

References

1. Blenrep approved by US FDA for use in treatment of relapsed/refractory multiple myeloma. News release. GSK. October 23, 2025. Accessed October 23, 2025. https://www.gsk.com/en-gb/media/press-releases/blenrep-approved-by-us-fda-for-use-in-treatment-of-relapsedrefractory-multiple-myeloma/

2. Hungria V, Robak P, Hus M, et al. Belantamab mafodotin, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2024;391(5):393-407. doi:10.1056/NEJMoa2405090

3. GSK announces extension of US Food and Drug Administration review period for Blenrep (belantamab mafodotin-blmf) in relapsed/refractory multiple myeloma. News release. GSK. July 23, 2025. Accessed October 23, 2025. https://www.gsk.com/en-gb/media/press-releases/gsk-announces-extension-of-us-food-and-drug-administration-review-period-for-blenrep-belantamab-mafodotin-blmf-in-relapsedrefractory-multiple-myeloma/