In a randomised, phase III DREAMM-7 study, treatment with belantamab mafodotin, bortezomib and dexamethasone (BVd regimen) conferred a significant benefit as compared with daratumumab, bortezomib and dexamethasone (DVd regimen) with respect to progression-free survival (PFS) among patients who had relapsed or refractory multiple myeloma after at least one line of therapy. The findings were reported at ASCO 2024 Annual Meeting along with a simultaneous publication by Dr. Maria-Victoria Mateos of the Hospital Universitario de Salamanca in Salamanca, Spain and colleagues on 1 June 2024 in The New England Journal of Medicine.
In a randomised, phase III DREAMM-8 study conducted among lenalidomide-exposed patients with relapsed or refractory myeloma, treatment with belantamab mafodotin, pomalidomide and dexamethasone (BPd regimen) conferred a significantly greater benefit as compared with pomalidomide, bortezomib and dexamethasone (PVd regimen) with respect to PFS. Ocular events were common, but were controllable by belantamab mafodotin dose modification. The findings were reported at ASCO 2024 Annual Meeting along with a simultaneous publication by Dr. Meletios Athanasios Dimopoulos of the Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens in Athens, Greece and colleagues on 2 June 2024 in The New England Journal of Medicine.
Patients with multiple myeloma are treated initially with triplet or quadruplet combination regimens that include proteasome inhibitors, immunomodulators, and anti-CD38 monoclonal antibodies. Most patients have disease progression after initial treatment, which highlights the need for efficacious second-line combinations that incorporate new therapeutics. BCMA is an established target for the treatment of multiple myeloma. Belantamab mafodotin is a BCMA-targeting antibody–drug conjugate with diverse mechanisms of antitumour activity.
DREAMM-7 study
In the phase III, open-label, randomised DREAMM-7 study, the investigators evaluated BVd regimen, as compared with DVd, in patients who had progression of multiple myeloma after at least one line of treatment. The primary endpoint was PFS. Key secondary endpoints were overall survival (OS), response duration, and minimal residual disease (MRD)–negative status.
A total of 494 patients were randomly assigned to receive BVd (243 patients) or DVd (251 patients). At a median follow-up of 28.2 months (range, 0.1 to 40.0), median PFS was 36.6 months (95% confidence interval [CI] 28.4 to not reached) in the BVd group and 13.4 months (95% CI 11.1 to 17.5) in the DVd group (hazard ratio [HR] for disease progression or death 0.41, 95% CI 0.31 to 0.53; p < 0.001).
At 18 months, the OS was 84% in the BVd group and 73% in the DVd group. An analysis of the restricted mean response duration favoured BVd over DVd (p < 0.001). A complete response or better plus MRD-negative status occurred in 25% of the patients in the BVd group and 10% of those in the DVd group.
Grade 3 or higher adverse events occurred in 95% of the patients in the BVd group and 78% of those in the DVd group. Ocular events were more common in the BVd group than in the DVd group (79% versus 29%); such events were managed with dose modifications, and events of worsening visual acuity mostly resolved. Approximately one quarter of the patients in the BVd group discontinued any of the three drugs in BVd because of treatment-related side effects.
The authors concluded that the strong results for PFS and the deep and durable response with BVd support the potential for BVd to become a treatment option for patients with multiple myeloma at or after the first relapse.
DREAMM-8 study
In the phase III, randomised, open-label DREAMM-8 study, the investigators evaluated BPd regimen, as compared with PVd, in lenalidomide-exposed patients who had relapsed or refractory multiple myeloma after at least one line of therapy. The primary endpoint was PFS. Disease response and safety were also assessed.
A total of 302 patients underwent randomisation; 155 were assigned to the BPd group, and 147 to the PVd group. At a median follow-up of 21.8 months (range, <0.1 to 39.2), the 12-month estimated PFS with BPd was 71% (95% CI 63 to 78), as compared with 51% (95% CI 42 to 60) with PVd (HR for disease progression or death 0.52, 95% CI 0.37 to 0.73; p < 0.001).
Data on OS were immature. Follow-up for OS is ongoing, and assessment of this outcome will be included in the planned subsequent interim and final OS analyses. The percentage of patients with a response to treatment (partial response or better) was 77% (95% CI 70 to 84) in the BPd group and 72% (95% CI 64 to 79) in the PVd group; 40% (95% CI, 32 to 48) and 16% (95% CI, 11 to 23), respectively, had a complete response or better.
Grade 3 or higher adverse events occurred in 94% of the patients in the BPd group and 76% of those in the PVd group. Ocular events occurred in 89% of the patients who received BPd (grade 3 or 4 in 43%) and 30% of those who received PVd (grade 3 or 4 in 2%). Ocular events in the BPd group were managed with belantamab mafodotin dose modification. Ocular events led to treatment discontinuation in 9% of the patients in the BPd group and in no patients in the PVd group.
The authors concluded that the results of DREAMM-8, together with DREAMM-7 conducted in a similar group of patients with relapsed or refractory multiple myeloma, highlight the potential of belantamab mafodotin–containing triplets to address the need for new regimens for the treatment of patients with multiple myeloma at first relapse.
The studies were funded by GSK.
References
- Hungria V, Robak P, Hus M, et al. for the DREAMM-7 Investigators. Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma. NEJM; Published online 1 June 2024. DOI: 10.1056/NEJMoa2405090
- Dimopoulos MA, Beksac M, Pour L, et al. for the DREAMM-8 Investigators. Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma. NEJM; Published 2 June 2024. DOI: 10.1056/NEJMoa240340