Belantamab Mafodotin Plus Lenalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma

Overview

The Phase 1/2 DREAMM-6 study Arm A evaluated belantamab mafodotin combined with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM). The combination demonstrated a 67% overall response rate with manageable safety, including frequent but mostly reversible ocular adverse events.

Background

Belantamab mafodotin is an anti-BCMA monoclonal antibody conjugated to a cytotoxic agent, showing synergistic activity with standard multiple myeloma therapies. Prior studies have demonstrated improved progression-free survival in RRMM when combined with other agents. DREAMM-6 Arm A investigated safety, tolerability, and efficacy of belantamab mafodotin with lenalidomide and dexamethasone in patients who had received at least one prior line of therapy.

Data Highlights

Key Findings

• No dose-limiting toxicities were observed during dose escalation across four dosing cohorts.
• Adverse events were universal, with keratopathy (53%), neutropenia (22%), thrombocytopenia (22%), and reduced visual acuity (22%) being the most common Grade 3/4 events.
• Ocular adverse events occurred in 80% of patients, with 69% experiencing Grade ≥3 events; 76% of these ocular events resolved over a median of 85.5 days.
• Serious adverse events occurred in 53% of patients, including four fatalities; one death due to febrile neutropenia was treatment-related.
• The overall response rate was 67%, with a complete response rate of 29% and median progression-free survival of 18.4 months.
• Minimal residual disease negativity was achieved in 15.6% of patients with complete response and 22.2% with very good partial response or better.

Clinical Implications

Belantamab mafodotin combined with lenalidomide and dexamethasone offers a promising therapeutic option for RRMM patients with manageable safety, particularly regarding ocular toxicity which requires monitoring but is largely reversible. The regimen yields substantial response rates and durable progression-free survival, supporting its consideration in patients with prior therapies including lenalidomide.

Conclusion

The DREAMM-6 Arm A results demonstrate that belantamab mafodotin plus lenalidomide and dexamethasone is an effective and tolerable treatment for relapsed or refractory multiple myeloma, with a favorable balance of efficacy and manageable adverse events, notably ocular toxicity.

References

1. Lonial et al. 2021 -- DREAMM-6 Study: Belantamab Mafodotin Combination Therapy in RRMM