RCT: Belantamab Mafodotin Combination Improves Progression-Free Survival in Relapsed/Refractory Multiple Myeloma Compared to Daratumumab-Based Therapy – N Engl J Med

Study Design and Population: This phase 3, open-label, randomized controlled trial compared the efficacy and safety of belantamab mafodotin, bortezomib, and dexamethasone (BVd) versus daratumumab, bortezomib, and dexamethasone (DVd) in 494 patients with relapsed or refractory multiple myeloma after at least one prior therapy. Patients were randomly assigned to the BVd group (243) or the DVd group (251) and were followed for a median of 28.2 months.

Main Findings: The BVd regimen significantly improved median progression-free survival (36.6 months vs. 13.4 months; HR, 0.41; P<0.001) compared to the DVd regimen. Overall survival at 18 months was also higher in the BVd group (84% vs. 73%). The BVd group showed a higher rate of complete response or better plus MRD-negative status (25% vs. 10%). However, the BVd regimen was associated with a higher incidence of grade 3 or higher adverse events (95% vs. 78%), particularly ocular events.

Implications for Practice: BVd therapy offers a significant progression-free survival advantage over DVd in patients with relapsed or refractory multiple myeloma, though it is associated with a higher rate of serious adverse events, particularly ocular toxicity. These findings suggest BVd as a potent treatment option but highlight the need for careful monitoring and management of side effects, particularly eye-related complications.

Reference: Hungria, V., Robak, P., Hus, M., Zherebtsova, V., Ward, C., Ho, P. J., & Ribas de Almeida, A. C., et al. (2024). Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma. New England Journal of Medicine, 391(5), 393-407. DOI: 10.1056/NEJMoa2405090.