Belantamab Mafodotin–Based Combos Win UK Approval for R/R Myeloma

Image credit:© Maris– stock.adobe.com

The United Kingdom’s (UK) Medicines and Healthcare products Regulatory Agency (MHRA) has approved belantamab mafodotin (Blenrep) in combination with bortezomib (Velcade) and dexamethasone (BVd) for the treatment of patients with relapsed/refractory multiple myeloma who have received at least 1 prior therapy; and in combination with pomalidomide (Pomalyst) and dexamethasone (BPd) for patients with relapsed/refractory multiple myeloma who have received at least 1 prior therapy, including lenalidomide (Revlimid).1

The regulatory decisions were supported by data from the phase 3 DREAMM 7 (NCT04246047) and DREAMM 8 (NCT04484623) trials, respectively.

“Today’s approval of [belantamab mafodotin] combinations in the UK is a transformative milestone for patients with multiple myeloma, a cancer marked by remission and relapse,” Hesham Abdullah, senior vice president and global head of Oncology, R&D, at GSK, stated in a news release. “As the only BCMA-targeted antibody-drug conjugate therapy, [belantamab mafodotin] has the potential, supported by robust phase 3 data, to extend survival and remission vs standard of care and redefine treatment at or after first relapse.”

In November 2024, the FDA accepted a biologics license application (BLA) seeking the approval of BVd and BPd for the treatment of patients with multiple myeloma who have received at least 1 prior line of therapy.2 The BLA was also supported by findings from DREAMM 7 and DREAMM 8.

DREAMM 7 Deep Dive

Findings from the randomized, open-label trial published in the New England Journal of Medicine showed that at a median follow-up of 28.2 months (range, 0.1-40.0), patients treated with BVd (n = 243) achieved a median progression-free survival (PFS) of 36.6 months (95% CI, 28.4-not reached [NR]) compared with 13.4 months (95% CI, 11.1-17.5) in patients treated with daratumumab (Darzalex) plus DVd (DVd; n = 251; HR, 0.41; 95% CI, 0.31-0.53; P < .001).3

The study enrolled patients at least 18 years of age with multiple myeloma who received at least 1 prior line of therapy and had documented disease progression during or after their most recent treatment.4 Other key inclusion criteria comprised measurable disease, an ECOG performance status of 0 to 2, and adequate organ function.

Patients were randomly assigned 1:1 to receive BVd or DVd. In the experimental arm, belantamab mafodotin was given at 2.5mg/kg once every 3 weeks.1 PFS served as the trial’s primary end point. Secondary end points included overall survival, duration of response, and minimal residual disease (MRD) negativity rate.

DREAMM-8 Overview

Findings from randomized, open-label trial also published in the New England Journal of Medicine demonstrated that at a median follow-up of 21.8 months (range, <0.1-39.2), BPd was associated with a 48% reduction in the risk of disease progression or death compared with PVd (HR, 0.52; 95% CI, 0.37-0.73; P < .001).5 The estimated 12-month PFS rates were 71% (95% CI, 63%-78%) for BPd (n = 155) vs 51% (95% CI, 42%-60%) with PVd (n = 147).

DREAMM-8 enrolled patients at least 18 years of age with multiple myeloma who were previously treated with at least 1 prior line of therapy, including a lenalidomide-containing regimen.6 Patients needed to have documented disease progression during or after their most recent therapy; they also needed to have an ECOG performance status of 0 to 2, measurable disease, and adequate organ function.

Patients were randomly assigned 1:1 to receive BPd or PVd. PFS was the trial’s primary end point, and secondary end points included OS, DOR, MRD-negativity rate, overall response rate, and safety.

DREAMMing of Safety Data

Safety results from both DREAMM 7 and DREAMM 8 showed that eye-related adverse effects (AEs) led to a treatment discontinuation rate of less than 9% in both studies, and these toxicities were generally resolvable and manageable with extended time between infusions and dose reductions.1

The most common AEs outside of ocular toxicity that were reported in more than 30% of participants treated with a belantamab mafodotin–based combination included thrombocytopenia (87%) and diarrhea (32%) in DREAMM 7, and neutropenia (63%), thrombocytopenia (55%) and COVID-19 (37%) in DREAMM 8.

References

1. Blenrep (belantamab mafodotin) combinations approved by UK MHRA in relapsed/refractory multiple myeloma. News release. GSK. April 17, 2025. Accessed April 17, 2025. https://www.gsk.com/en-gb/media/press-releases/blenrep-belantamab-mafodotin-combinations-approved-by-uk-mhra-in-relapsedrefractory-multiple-myeloma/
2. Blenrep combinations accepted for review by the US FDA for the treatment of relapsed/refractory multiple myeloma. News release. GSK. November 25, 2024. Accessed April 17, 2025. https://www.gsk.com/en-gb/media/press-releases/blenrep-combinations-accepted-for-review-by-the-us-fda-for-the-treatment-of-relapsedrefractory-multiple-myeloma/
3. Hungria V, Robak P, Hus M, et al. Belantamab mafodotin, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2024;391(5):393-407. doi:10.1056/NEJMoa2405090
4. Evaluation of efficacy and safety of belantamab mafodotin, bortezomib and dexamethasone versus daratumumab, bortezomib and dexamethasone in participants with relapsed/​refractory multiple myeloma (DREAMM 7). ClinicalTrials.gov. Updated October 24, 2024. Accessed April 17, 2025. https://clinicaltrials.gov/study/NCT04246047
5. Dimopoulos MA, Beksac M, Pour L, et al. Belantamab mafodotin, pomalidomide, and dexamethasone in multiple myeloma. N Engl J Med. 2024;391(5):408-421. doi:10.1056/NEJMoa2403407
6. Belantamab mafodotin plus pomalidomide and dexamethasone (Pd) versus bortezomib plus Pd in relapsed/​refractory multiple myeloma (DREAMM 8). ClinicalTrials.gov. Updated March 18, 2025. Accessed April 17, 2025. https://clinicaltrials.gov/study/NCT04484623