EU Approves Belantamab Mafodotin Combinations for Relapsed/Refractory Myeloma

The European Union (EU) has granted approval for belantamab mafodotin (Blenrep) in combination with established regimens for the treatment of adult patients with relapsed or refractory multiple myeloma. This significant regulatory milestone provides new therapeutic options for a patient population with substantial unmet needs, particularly for those who have received at least 1 prior therapy.¹

The approvals are specifically for belantamab mafodotin in combination with bortezomib and dexamethasone (BVd) and in combination with pomalidomide and dexamethasone (BPd), representing an important advancement in the sequential treatment landscape for this complex hematologic malignancy.

The decision from the European Commission is based on compelling data derived from the pivotal phase 3 DREAMM-7 (NCT04246047) and DREAMM-8 (NCT04484623) clinical trials. These studies demonstrated superior efficacy for the belantamab mafodotin-containing combinations compared to current standard-of-care triplet regimens, showcasing statistically significant and clinically meaningful improvements in progression-free survival (PFS). Notably, the DREAMM-7 trial also exhibited an overall survival (OS) benefit, a critical endpoint in advanced cancer settings, against a daratumumab (Darzalex)-based triplet.

Multiple myeloma remains an incurable plasma cell disorder characterized by cycles of remission and relapse, often necessitating a continuous search for novel and effective therapies. Patients with relapsed or refractory disease, especially those who have been heavily pretreated, face particularly challenging prognoses. The introduction of belantamab mafodotin, an antibody-drug conjugate (ADC) targeting BCMA, offers a distinct mechanism of action within the myeloma armamentarium. BCMA is a protein highly expressed on malignant plasma cells, making it an attractive target for therapeutic intervention. Belantamab mafodotin selectively delivers a potent cytotoxic agent, MMAF, directly to BCMA-expressing myeloma cells, leading to their apoptosis.

In the DREAMM-7 study (NCT04246047), BVd was compared against daratumumab in combination with bortezomib and dexamethasone (DVd) in patients who had received at least 1 prior therapy. The trial enrolled 494 participants. The updated analysis, with a median follow-up of 39.4 months, revealed a statistically significant overall survival benefit for the BVd arm (median OS not reached) compared to the DVd arm (median OS, 41.0 months), with a hazard ratio (HR) of 0.58 (95% CI, 0.43–0.79; P =.0002). Furthermore, BVd demonstrated greater than double the minimal residual disease (MRD) negativity rates in patients achieving a complete response or better (25% vs 10%) and a significantly longer median duration of response (40.8 months vs 17.8 months).

The DREAMM-8 study (NCT04484623) evaluated BPd vs bortezomib, pomalidomide, and dexamethasone (PVd) in patients with relapsed or refractory multiple myeloma who had received at least one prior therapy, including lenalidomide. This cohort was generally more heavily pretreated than those in DREAMM-7, with a high proportion of patients refractory to lenalidomide. The BPd combination demonstrated superior progression-free survival compared to PVd, offering a meaningful benefit in this challenging patient population.

The safety profiles of the belantamab mafodotin combinations in these trials were consistent with the known safety profile of the individual agents. The most commonly reported nonocular adverse events (>30% of participants) in the belantamab mafodotin combination arms included thrombocytopenia and diarrhea in DREAMM-7 and neutropenia, thrombocytopenia, and COVID-19 in DREAMM-8. Ocular toxicity, specifically keratopathy, is a known and monitored side effect of belantamab mafodotin, requiring close ophthalmic monitoring. This necessitates a proactive approach to patient management, including regular eye examinations and potential dose modifications or interruptions to manage ocular adverse events.

In the US, the FDA’s Oncologic Drug Advisory Committee (ODAC) voted on July 17, 2025, that the benefit-risk profile of belantamab mafodotin at its proposed dosage was not favorable.² The Prescription Drug User Fee Act target action date for the application of belantamab mafodotin was July 23, 2025.

The approval of belantamab mafodotin combinations marks a pivotal moment for multiple myeloma treatment in the EU. As stated by María-Victoria Mateos, MD, head of the Myeloma and Clinical Trials Unit at the University of Salamanca, Spain, and a principal investigator for DREAMM-7, “With the approval of [belantamab mafodotin] combinations in the EU, we now have additional tools in our efforts to keep patients in remission longer, maintain quality of life, and extend survival. The robust efficacy supported by the DREAMM-7 and DREAMM-8 trials, together with manageable outpatient administration in academic and community settings, positions [belantamab mafodotin] combinations as a fundamentally differentiated treatment approach for multiple myeloma patients starting from first relapse.”¹

The ability to administer belantamab mafodotin in both academic and community-based settings, along with its differentiated mechanism of action as the only anti-BCMA ADC approved in multiple myeloma, offers increased flexibility and accessibility for clinicians and patients.

REFERENCES:

1. Blenrep (belantamab mafodotin) combinations approved in EU for treatment of relapsed/refractory multiple myeloma. News release. GSK. July 24, 2025. Accessed July 24, 2025. https://tinyurl.com/2tnym3w4 

2. Meeting of the Oncologic Drug Advisory Committee. FDA. July 17, 2025. Accessed July 17, 2025. https://tinyurl.com/bdf6dfuk