Belantamab Mafodotin Plus Bortezomib and Dexamethasone Demonstrates Clinical Activity in Relapsed or Refractory Multiple Myeloma
Clinical Summary:
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Design/Population: The phase 1/2 DREAMM-6 study evaluated belantamab mafodotin in combination with bortezomib and dexamethasone across multiple dosing schedules in 107 heavily pretreated patients with relapsed or refractory multiple myeloma.
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Key Outcomes: The combination achieved an overall response rate of 70%, with no dose-limiting toxicities observed. Ocular adverse events, including keratopathy, were common across dosing cohorts, although exposure-response analyses identified a regimen that balanced efficacy and safety.
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Clinical Relevance: These findings support the 2.5 mg/kg every-3-week dosing schedule of belantamab mafodotin in combination with bortezomib and dexamethasone while underscoring the importance of proactive ophthalmologic monitoring during treatment.
Results from Arm B of the phase 1/2 DREAMM-6 study demonstrated that belantamab mafodotin in combination with bortezomib and dexamethasone produced durable clinical activity across multiple dosing schedules in heavily pretreated patients with relapsed or refractory multiple myeloma, while identifying a dose that balanced efficacy and safety.
In this study, 107 adults with relapsed or refractory multiple myeloma were enrolled into sequential dose-escalation and dose-expansion cohorts evaluating multiple belantamab mafodotin dosing schedules in combination with bortezomib and dexamethasone. The primary end points were dose-limiting toxicities, safety, and overall response rate (ORR).
During dose escalation, patients initially received belantamab mafodotin at 2.5 mg/kg followed by 3.4 mg/kg every 3 weeks in combination with bortezomib and dexamethasone. Dose-expansion cohorts subsequently evaluated multiple dosing strategies, including every-3-week, split-dose, every-6-week, and step-down schedules.
No dose-limiting toxicities were observed during dose escalation. Across all dosing cohorts, the ORR was 70%.
The most common grade ≥3 adverse event was keratopathy (53%). Protocol-defined ocular adverse events occurred in 93% of patients, including grade ≥3 events in 77% of patients. Treatment-related serious adverse events occurred in 26% of patients, including 3 treatment-related deaths among 7 fatal serious adverse events.
Exposure-response analyses demonstrated that higher initial belantamab mafodotin exposure was associated with both improved response rates and increased ocular toxicity. Lower-exposure regimens reduced the frequency of deep responses while producing only modest reductions in ocular adverse events.
Source:
Popat R, Augustson B, Cannell P, et al. Efficacy and safety of belantamab mafodotin with bortezomib plus dexamethasone in patients with relapsed/refractory multiple myeloma: The DREAMM-6 arm B trial. Clin Cancer Res. Published online: March 2, 2026. doi: 10.1158/1078-0432.CCR-25-3216
