Belantamab Mafodotin Combinations Approved in EU and Canada for Myeloma

On July 24, 2025, the European Commission and Health Canada granted approval for belantamab mafodotin (Blenrep) in combination with bortezomib (Velcade) and dexamethasone (BVd), as well as with pomalidomide (Pomalyst) and dexamethasone (BPd), to treat adult patients with relapsed or refractory multiple myeloma (R/R MM) who have undergone at least one prior therapy. These approvals follow the positive results of two pivotal Phase 3 trials, DREAMM-7 and DREAMM-8, which demonstrated significant improvements in progression-free survival (PFS) compared to standard treatment regimens.

The DREAMM-7 trial involved 402 participants and found that the BVd combination achieved a median PFS of 36.6 months, significantly better than the 13.4 months reported for daratumumab plus bortezomib and dexamethasone (DVd). The hazard ratio (HR) for this comparison was 0.41, with a p-value of less than 0.00001, indicating a statistically significant difference. Additionally, the trial showed a 42% reduction in the risk of death for patients receiving the BVd combination, with a median follow-up of 39.4 months. Notably, the 3-year overall survival rate was 74% for the BVd group compared to 60% for the DVd group.

Similarly, the DREAMM-8 trial, which evaluated the BPd regimen, reported a median PFS that was not reached (NR) at a median follow-up of 21.8 months, contrasting with 12.7 months for bortezomib plus pomalidomide and dexamethasone (PVd). Both trials underscored the efficacy of belantamab mafodotin combinations, positioning them as potential game-changers in the treatment of R/R MM.

Dr. María-Victoria Mateos, a prominent figure in the field and head of the Myeloma and Clinical Trials Unit at the University of Salamanca, remarked, "With the approval of belantamab mafodotin combinations in the European Union, we now have additional tools in our efforts to keep patients in remission longer, maintain quality of life and extend survival." Her insights reflect the optimism surrounding these new treatment options, particularly in an area where historic treatment regimens have often yielded limited success.

Safety data from both trials indicated that ocular adverse effects, commonly associated with belantamab mafodotin, were largely manageable and reversible with proper dose adjustments and routine ophthalmologic monitoring. Less than 9% of patients discontinued treatment due to eye-related toxicities. Non-ocular adverse events included thrombocytopenia (87%) and diarrhea (32%) in DREAMM-7, while DREAMM-8 reported neutropenia (63%), thrombocytopenia (55%), and a notable incidence of COVID-19 (37%). These safety profiles align with known effects of the individual drugs used in the combinations.

Despite these approvals, the path to U.S. approval remains uncertain. On July 17, 2025, the FDA’s Oncologic Drugs Advisory Committee (ODAC) did not endorse the risk-benefit profiles for the proposed doses of belantamab mafodotin. The committee voted 5 to 3 against the BVd combination and 7 to 1 against the BPd combination, citing concerns over the safety and efficacy data presented. Following this decision, GSK announced an extension of the review period for the biologics license application in the U.S., with a new action date set for October 23, 2025.

As the landscape of multiple myeloma treatment evolves, the international approvals of belantamab mafodotin-based therapies could signal a pivotal shift in managing this challenging disease. Stakeholders remain hopeful that continued research and regulatory dialogue will pave the way for broader access to these promising therapies, ultimately enhancing patient outcomes in the fight against relapsed and refractory multiple myeloma.