The combination of belantamab mafodotin (Blenrep), bortezomib (Velcade), and dexamethasone (BVd) has demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared to daratumumab (Darzalex) plus bortezomib and dexamethasone (DVd) in patients with relapsed/refractory multiple myeloma. These findings from the phase 3 DREAMM-7 trial (NCT04246047) were presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition and suggest a potential paradigm shift in the treatment of this challenging disease.
The DREAMM-7 trial, a multi-center, open-label, randomized study, enrolled 494 patients with relapsed/refractory multiple myeloma who had received at least one prior line of therapy. Participants were randomized 1:1 to receive either BVd or DVd. Belantamab mafodotin was administered intravenously at 2.5 mg/kg every three weeks.
Significant Overall Survival Benefit
At a median follow-up of 39.4 months, the BVd arm (n=243) showed a statistically significant 42% reduction in the risk of death compared to the DVd arm (n=251) (HR 0.58; 95% CI: 0.43-0.79; p=0.00023). Although the median overall survival (mOS) was not reached in either arm, post hoc analysis projected a mOS of 84 months for BVd compared to 51 months for DVd. The three-year OS rate was 74% in the belantamab mafodotin combination arm and 60% in the daratumumab combination arm.
According to María-Victoria Mateos, MD, PhD, Head of Myeloma and Clinical Trials Unit, Hematology Department and Professor of Medicine at the University of Salamanca, Spain, and DREAMM-7 principal investigator, "The totality of evidence from DREAMM-7 represents a potential paradigm shift for multiple myeloma patients who have experienced a relapse or become refractory to initial treatment."
Key Secondary Endpoints
The belantamab mafodotin combination also demonstrated statistically significant superiority on the key secondary endpoint of minimal residual disease (MRD) negativity (no detectable cancer cells) compared to the daratumumab combination. The rate of MRD negativity was more than 2.5-fold higher in the BVd arm (p<0.00001).
In addition to OS and MRD negativity, the belantamab mafodotin combination resulted in clinically meaningful improvements in all key secondary efficacy endpoints compared to the daratumumab combination, including duration of response (DOR) and progression-free survival 2 (PFS 2). The results indicate deeper and more durable responses among patients treated with BVd compared to DVd.
Safety and Tolerability
The safety and tolerability of the belantamab mafodotin regimen were consistent with the primary analysis and known safety profile of the individual agents. Grade 3 or higher adverse events of clinical interest in the belantamab mafodotin combination and daratumumab combination arms, respectively included thrombocytopenia (56% versus 35%); anemia (9% versus 10%); and neutropenia (14% versus 10%). Eye-related side effects, a known risk of treatment with belantamab mafodotin, were generally manageable and resolvable with dose modification, and led to a low (10%) treatment discontinuation rate.
Regulatory Landscape
Regulatory filings for belantamab mafodotin combinations for the treatment of relapsed or refractory multiple myeloma based on the results of the DREAMM-7 and DREAMM-8 trials have been accepted in the US, European Union, Japan (with priority review), China (for DREAMM-7 only, with priority review; Breakthrough Therapy Designation also granted), United Kingdom, Canada and Switzerland (with priority review for DREAMM-8).
Linvoseltamab Shows Durable Efficacy
In a separate study, linvoseltamab, a BCMA and CD3 bispecific antibody, demonstrated durable efficacy and manageable safety in patients with relapsed/refractory multiple myeloma. Follow-up results from the phase 1/2 LINKER-MM1 study (NCT03761108) presented at the 66th ASH Annual Meeting showed an overall response rate of 71% and a complete response rate or better of 52% at a median follow-up of 21.3 months. Cytokine release syndrome (CRS) occurred in 46% of patients, but resolved within 14.7 hours. The median duration of response was 29 months, the median PFS was not reached, and the median overall survival was 31 months.
Implications for Treatment
The DREAMM-7 trial results suggest that the belantamab mafodotin combination could become a new standard of care for patients with relapsed or refractory multiple myeloma. The statistically significant and clinically meaningful improvement in overall survival, coupled with improvements in other key endpoints, supports the use of this regimen in this patient population. The ongoing DREAMM clinical development program continues to evaluate the potential of belantamab mafodotin in earlier lines of treatment and in combination with novel therapies and standard of care treatments.
