The phase III DREAMM-7 study, presented at the ASCO Plenary Series: February 2024, revealed that the belantamab mafodotin, bortezomib, and dexamethasone (BVd) regimen significantly improves progression-free survival in patients with relapsed or refractory multiple myeloma compared to daratumumab, bortezomib, and dexamethasone (DVd). The study enrolled 494 patients and demonstrated a clinically meaningful and statistically significant improvement in progression-free survival, with a strong trend toward better overall survival with BVd.
Superior Progression-Free Survival with BVd
The DREAMM-7 trial randomly assigned patients with multiple myeloma, who had received at least one prior line of therapy, to either the BVd or DVd regimen. Belantamab mafodotin was administered at 2.5 mg/kg every 3 weeks. The primary endpoint was progression-free survival. After a median follow-up of 28.2 months, the median progression-free survival was 36.6 months in the BVd arm compared to 13.4 months in the DVd arm (HR = 0.41; P < .0001). This progression-free survival benefit was consistently observed across various prespecified subgroups, including patients with lenalidomide-refractory (HR = 0.37) or high-risk cytogenetic (HR = 0.36) myeloma.
Overall Survival Trend and Response Rates
An early and clinically meaningful trend favoring the BVd arm was observed for overall survival. Median overall survival was not reached in either arm, with events recorded for 22% of the BVd arm and 35% of the DVd arm (HR = 0.57; P = .00049). The threshold for statistical significance was P ≤ .00037, and follow-up for overall survival is ongoing. The BVd regimen was also associated with a doubling in response rates and undetectable measurable residual disease. At 18 months, 76% of the BVd arm and 49% of the DVd arm were still responding to treatment.
Safety and Tolerability
Serious adverse events occurred in 50% of patients treated with BVd compared to 37% of those treated with DVd, with higher drug exposure in the BVd arm. The safety and tolerability of the BVd regimen were generally consistent with the known safety profiles of the individual agents. Ocular adverse effects, a known concern with belantamab mafodotin, were observed in 79% of the BVd arm and 29% of the DVd arm, with grade ≥ 3 events in 34% and 3%, respectively. These primarily included blurred vision (66% overall, 22% grade ≥ 3), dry eyes, eye irritation, and visual impairment (grade ≥ 3 in ≤ 7%). Ocular complaints led to dose reductions in 44%, dose interruptions in 78%, and treatment discontinuation in 9% of the BVd arm; however, these effects were reported to be reversible in almost all patients. No significant difference was observed in global quality of life over time between the arms.
Implications for Treatment
According to Dr. Maria-Victoria Mateos Manteca, MD, PhD, Associate Professor of Medicine at the University of Salamanca, the results suggest that BVd has the potential to become a new standard of care in second-line or later relapsed and refractory multiple myeloma, due to its robust efficacy, manageable safety, and ease of administration. This recommendation applies irrespective of prior exposure to immunomodulatory drugs or proteasome inhibitors.
Belantamab mafodotin is an antibody-drug conjugate targeting B-cell maturation antigen (BCMA).
