“To our knowledge, this is the first phase 3, randomised, head-to-head study showing such robust [OS] benefit with a triplet regimen against an established daratumumab-based regimen in patients with [relapsed/refractory multiple myeloma] who have received at least 1 previous line of therapy, further supporting the use of BVd as a potential new standard of care for these patients,” according to the study authors.
Combining belantamab mafodotin-blmf (Blenrep) with dexamethasone and bortezomib (Velcade; BVd) demonstrated clinically meaningful and statistically significant improvements in outcomes like overall survival (OS) and progression-free survival (PFS) among patients with relapsed/refractory multiple myeloma, according to updated findings from the phase 3 DREAMM-7 trial (NCT04246047) published in Lancet Oncology.1
The median OS was not reached (NR; 95% CI, NR-NR) with BVd and NR (95% CI, 41.0-NR) with daratumumab (Darzalex) plus bortezomib and dexamethasone (DVd; HR, 0.58; 95% CI, 0.43-0.79; P = .0002). In each respective arm, the 24-month OS rates were 79% (95% CI, 73%-84%) vs 67% (95% CI, 61%-73%), and the 36-month rates were 74% (95% CI, 68%-79%) vs 60% (95% CI, 54%-66%). Across prespecified subgroups, BVd demonstrated OS benefits in patients with prior exposure to lenalidomide (Revlimid), those with lenalidomide-refractory disease, and those with high-risk cytogenetics.
Data showed an objective response rate (ORR) of 83% (95% CI, 77.8%-87.6%) with BVd vs 71% (95% CI, 65.3%-76.8%) with DVd, with 36% (95% CI, 29.8%-42.2%) and 18% (95% CI, 13.0%-22.8%) in each arm achieving a complete response (CR) or better. Minimal residual disease (MRD) negativity occurred in 25% (95% CI, 19.8%-31.0%) and 10% (95% CI, 6.9%-14.8%) of patients with a CR or better, with sustained MRD-negative status for at least 12 months reported in 14% (95% CI, 10.2%-19.5%) and 4% (95% CI, 2.2%-7.7%) of patients with a CR or better. BVd produced a median duration of response (DOR) of 40.8 months (95% CI, 30.5-NR) vs 17.8 months (95% CI, 13.8-23.6) with DVd.
Regarding PFS2, which was defined as the time from randomization to disease progression following the initiation of any subsequent antimyeloma therapy or death from any cause, events occurred in 38% of the BVd arm and 50% of those in the DVd arm. Additionally, the median PFS2 was NR (95% CI, 45.6-NR) and 33.4 months (95% CI, 26.7-44.9) in each arm (HR, 0.59; 95% CI, 0.45-0.77).
“DREAMM-7 showed significant and clinically meaningful [OS], [PFS], [MRD] negativity, and [DOR] benefits with BVd compared with DVd. The safety profile of BVd was consistent with that in the primary analysis, with no new safety concerns,” lead study author Vania Hungria, MD, PhD, from the Department of Hematology at Clinica São Germano in São Paulo, Brazil, wrote with coauthors.1 “To our knowledge, this is the first phase 3, randomised, head-to-head study showing such robust [OS] benefit with a triplet regimen against an established daratumumab-based regimen in patients with [relapsed/refractory multiple myeloma] who have received at least 1 previous line of therapy, further supporting the use of BVd as a potential new standard of care for these patients.”
In the open-label DREAMM-7 trial, 494 patients were randomly assigned to receive BVd (n = 243) or DVd (n = 251). Investigators administered belantamab mafodotin at 2.5 mg/kg intravenously every 3 weeks and daratumumab at 16 mg/kg intravenously once weekly in cycles 1 to 3, every 3 weeks in cycles 4 to 8, and every 4 weeks thereafter. Additionally, all patients received bortezomib at 1.3 mg/m2 subcutaneously twice weekly for 8 cycles plus dexamethasone at 20 mg orally or intravenously on the day of and day after bortezomib.
The trial’s primary end point was PFS. Secondary end points included OS, MRD negativity in patients with a CR or better, DOR, and safety. Patients 18 years and older with a confirmed multiple myeloma diagnosis based on International Myeloma Working Group criteria, at least 1 prior line of treatment, documented disease progression on or after the most recent line of therapy, and an ECOG performance status of 0 to 2 were eligible for enrollment on the trial.
The median age was 64.5 years (IQR, 57.0-71.0) across both treatment groups, and most patients were male (55%) and White (83%). Overall, baseline characteristics were balanced across the BVd and DVd arms. The median follow-up at the time of this analysis was 39.4 months (range, 0.1-52.3).
Investigators noted receipt of any subsequent therapy in 36% of the BVd arm and 52% of the DVd arm. In each respective arm, the most common types of subsequent treatment included steroids (32% vs 43%), dexamethasone (31% vs 42%), and immunomodulators (25% vs 37%).
Any-grade adverse effects (AEs) affected 100% of the BVd and the DVd arms, with grade 3/4 toxicities occurring in 95% vs 78%. In each arm, 32% vs 19% had toxicities leading to treatment discontinuation, 75% vs 59% had AEs resulting in dose reductions, and 95% vs 76% had toxicities associated with dose delays. Investigators reported fatal serious AEs in 11% of the BVd arm and 8% of the DVd arm.
Thrombocytopenia was the most common grade 3/4 toxicity and occurred in 56% of the BVd arm compared with 35% of the DVd arm. The most common ocular toxicities in the BVd arm included dry eyes (53%), photophobia (50%), foreign body sensations in the eyes (46%), and eye irritation (45%).
In July 2025, the FDA’s Oncologic Advisory Drug Committee (ODAC) voted 5-3 against the favorability of BVd as a treatment for patients with multiple myeloma following at least 1 prior line of therapy.2
References
- Hungria V, Robak P, Hus M, et al. Belantamab mafodotin plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-7): updated overall survival analysis from a global, randomised, open-label, phase 3 trial. Lancet Oncol. Published online July 15, 2025. doi:10.1016/S1470-2045(25)00330-4
- July 17, 2025, Meeting of the Oncologic Drugs Advisory Committee (ODAC). FDA. Streamed live July 17, 2025. Accessed July 23, 2025. https://tinyurl.com/mhafuuy8