Belantamab mafodotin has been approved in the European Union (EU) for the treatment of adults with relapsed or refractory multiple myeloma in combination with bortezomib plus dexamethasone (BVd) in patients who have received at least one prior therapy, and in combination with pomalidomide plus dexamethasone (BPd) in patients who have received at least one prior therapy including lenalidomide.

The approval is based on superior efficacy results demonstrated by belantamab mafodotin combinations in the pivotal DREAMM-7 and DREAMM-8 phase III trials in relapsed or refractory multiple myeloma. These include statistically significant and clinically meaningful progression-free survival (PFS) for Blenrep combinations versus triplet standard of care combinations in both trials and overall survival (OS) versus a daratumumab-based triplet in DREAMM-7. The safety and tolerability profiles of the Blenrep combinations were broadly consistent with the known profiles of the individual agents.

Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: “Today’s approval of belantamab mafodotin combinations is a redefining moment for patients with relapsed or refractory multiple myeloma in the EU. Belantamab mafodotin has the potential to extend remission and survival, with superior efficacy versus standards of care in our DREAMM clinical trial programme and the option to administer in both academic and community-based settings.”
 
More than 50,000 cases of multiple myeloma are diagnosed in Europe each year, accounting for more than a quarter of global incidence. Belantamab mafodotin is the only anti-BCMA (B-cell maturation antigen) antibody-drug conjugate (ADC) approved in multiple myeloma, providing patients with a differentiated mechanism of action to potentially help slow disease progression and extend survival. Belantamab mafodotin combinations can be administered to a range of patient types across oncology treatment settings, enabling broad accessibility of an anti-BCMA therapy. 

María-Victoria Mateos, MD, PhD, Head of Myeloma and Clinical Trials Unit, Haematology Department and Professor of Medicine at the University of Salamanca, Spain, and DREAMM-7 principal investigator, said: “With the approval of Blenrep 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.”

Both DREAMM-7 and DREAMM-8 showed statistically significant and clinically meaningful PFS improvements for the belantamab mafodotin combinations compared to standard of care triplet combinations in the second line or later treatment of multiple myeloma. In DREAMM-7, the belantamab mafodotin combination (n=243) nearly tripled median PFS versus the daratumumab-based comparator (n=251) (36.6 months versus 13.4 months, respectively (hazard ratio [HR]: 0.41 [95% confidence interval (CI): 0.31-0.53], p-value<0.00001).2 DREAMM-7 also met the key secondary endpoint of OS, showing a statistically significant and clinically meaningful 42% reduction in the risk of death at a median follow-up of 39.4 months favouring the belantamab mafodotin combination versus the daratumumab-based comparator (HR: 0.58; 95% CI: 0.43-0.79; p=0.00023). The median OS was not reached in either arm of the study. The three-year OS rate was 74% in the belantamab mafodotin combination arm and 60% in the daratumumab combination arm. In DREAMM-8, at a median follow-up of 21.8 months, the median PFS was not yet reached (95% CI: 20.6-not yet reached [NR]) with the belantamab mafodotin combination compared to 12.7 months in the bortezomib combination (95% CI: 9.1-18.5) at the time of primary analysis.

Blenrep combinations consistently benefited a broad range of patients, including those with poor prognostic features or outcomes, such as high-risk cytogenetics or those refractory to lenalidomide. Both trials also showed clinically meaningful improvements across all other secondary efficacy endpoints, including deeper and more durable responses versus the respective comparators.

DREAMM-7 and DREAMM-8 showed that eye-related side effects associated with belantamab mafodotin can be managed and reversed with appropriate dose modifications and follow-up. This allowed patients to maintain benefit and resulted in low rates of discontinuation due to eye-related side effects (≤9%) in both trials.The most commonly reported non-ocular adverse events (>30% of participants) in the belantamab mafodotin combination arm were thrombocytopenia (87%) and diarrhoea (32%) in DREAMM-7, and neutropenia (63%), thrombocytopenia (55%) and COVID-19 (37%) in DREAMM-8.

Belantamab mafodotin combinations are also approved in relapsed or refractory multiple myeloma in the UK and Japan as well as other markets, including Canada and Switzerland (based on the results of DREAMM-8). Applications are currently under review in all major markets globally, including the US and China (based on the results of DREAMM-7, with Breakthrough Therapy Designation for the combination and priority review for the application).

Source: GSK