UK MHRA approves belantamab mafodotin in combination with Vd and Pd for RRMM

On April 17, 2025, the UK Medicines and Healthcare products Regulatory Agency (MHRA) approved belantamab mafodotin, a B-cell maturation antigen (BCMA)-directed antibody–drug conjugate (ADC), in combination with bortezomib and dexamethasone (BVd) for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) and ≥1 prior therapy, and in combination with pomalidomide and dexamethasone (BPd) for patients with RRMM and ≥1 prior therapy including lenalidomide.

These approvals were based on data from the phase III DREAMM-7 (NCT04246047) and DREAMM-8 (NCT04484623) trials, respectively, and mark the first regulatory approval for belantamab mafodotin in these indications, globally.

DREAMM-7 pivotal data^1,2

• The median progression-free survival (PFS) was 36.6 months for patients treated with BVd, compared with 13.4 months for those treated with daratumumab, bortezomib, and dexamethasone (DVd).
  • This corresponded to a hazard ratio (HR) of 0.41 (95% confidence interval [CI]: 0.31–0.53; p < 0.00001), indicating a 59% reduction in the risk of disease progression or death.
• DREAMM-7 also met its secondary endpoint of overall survival (OS). At a median follow-up of 39.4 months, patients treated with BVd experienced a 42% reduction in the risk of death compared with those treated with DVd (HR 0.58; 95% CI: 0.43–0.79; p = 0.00023).
  • At 3 years, the OS rate was 74% with BVd and 60% with DVd.
• Ocular adverse events (AEs) were generally manageable with strategies such as dose reductions and extended treatment-free intervals, with no compromise in efficacy; they led to treatment discontinuation in ≤9% of patients.
• The most common non-ocular AEs in the BVd cohort were thrombocytopenia in 87% and diarrhea in 32%.
• The BVd regimen was also effective across a range of patient subgroups, including those with high-risk cytogenetic features and those refractory to lenalidomide.

DREAMM-8 pivotal data^1,3

• At a median follow-up of 21.8 months, the median PFS with BPd had not yet been reached, compared with 12.7 months in the pomalidomide, bortezomib, and dexamethasone (PVd) arm.
• Ocular AEs were generally manageable with supportive care measures, resulting in ≤9% of patients discontinuing treatment.
• The most common non-ocular AEs in the BPd cohort were neutropenia in 63%, thrombocytopenia in 55%, and COVID-19 infections in 37%.
• The BPd regimen was also effective across a range of patient subgroups, including those with high-risk cytogenetics and those resistant to previous treatments.