Belantamab Mafodotin Achieves Secondary End Point for Treatment of Relapsed, Refractory Multiple Myeloma

Belantamab mafodotin (Blenrep; GSK) in combination with bortezomib (Velcade; Millennium/Takeda, Janssen Pharmaceutical Companies) and dexamethasone demonstrated clinically meaningful reductions in risk of death in the second line for patients with relapsed or refractory multiple myeloma (RRMM). According to results from the DREAMM-7 trial (NCT04246047), the treatment met its key secondary end point of overall survival (OS).¹

Multiple myeloma cells depiction | Image Credit: © DZMITRY - stock.adobe.com

MM is a common, incurable hematologic malignancy characterized by periods of remission followed by relapse, in which outcomes typically worsen with each successive line of therapy. Although significant advancements in treatment help overcome mutations and may prolong remission periods, an unmet need remains for patients who relapse. According to study results published in Leukemia, found the median time to relapse after first line treatment was 26.9.²

The development of immunotherapies and other novel agents has significantly improved health outcomes for patients with RRMM, with approved therapies in the first, second, and later lines. Belantamab mafodotin is an anti-BCMA antibody-drug conjugate approved by the FDA in August 2020 based on results from the phase 2 DREAMM-2 trial (NCT03525678); however, it was pulled from the market in November 2022 after it didn’t meet its primary end point of progression free survival in the DREAMM-3 trial (NCT04162210).^3-5

“We respect the agency’s approach to the accelerated approval regulations and associated process,” said Sabine Luik, Chief Medical Officer at GSK, following the FDA’s decision. “[MM] is a challenging disease, with poor outcomes for patients whose disease has become resistant to standard-of-care treatments. We will continue the DREAMM clinical trial program and work with the US FDA on a path forward for this important treatment option for patients with [MM].”⁶

Investigations into treatment of RRMM with belantamab mafodotin have continued in the DREAMM clinical trial program, which aims to determine the benefit of the agent in combination treatment with novel therapies and standard-of-care treatments. In the multicenter, open-label, randomized, phase 3 DREAMM-7 trial, researchers evaluated the safety and efficacy of belantamab mafodotin in combination with bortezomib and dexamethasone (BVd) compared with daratumumab (Darzalex; Johnson &Johnson), bortezomib, and dexamethasone (DVd).^6,7

The trial involved 494 patients with RRMM who had progressed after at least 1 prior line of treatment. They were randomized 1:1 to receive either BVd (n=243) or DVd (n=251), in which belantamab mafodotin was administered at 2.5mg/kg intravenously every 3 weeks. The primary end point of the study was PFS with secondary end points including OS, duration of response, and minimal residual disease (MRD) negativity rate, as well as safety and quality-of-life outcomes.⁸

The data showed that median PFS was 36.6 months (95% confidence interval [CI], 28.4 to not reached) in the BVd group and 13.4 months (95% CI, 11.1 to 17.5) in the DVd group (hazard ratio for disease progression or death, 0.41; 95% CI, 0.31 to 0.53; P<0.001) at a median follow-up of 28.2 months. Belantamab mafodotin demonstrated additional benefits in OS. Patients receiving BVd had an OS of 84% at 18 months compared with 73% in the DVd group. A complete response or better plus MRD-negative status occurred in 25% of the patients in the BVd group and 10% of those in the DVd group.⁸

Regarding the safety of BVd, the majority of adverse events (AEs) were grade 3 or higher, occurring in 95% of the patients in the BVd group and 78% of those in the DVd group. Ocular events were more prevalent in patients receiving BVd (79%) verses DVd (29%). Dose modifications were effective in managing AEs.⁸

The data suggests potential benefits of treatment with BVd, offering patients a larger catalogue of alternative therapies as they navigate their treatment and the heterogeneity of MM.

REFERENCES

1. 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 Identifier: NCT04246047. Updated October 24, 2024. Accessed November 22, 2024. https://clinicaltrials.gov/study/NCT04246047

2. Majithia N, Rajkumar SV, Lacy MQ, et al. Early relapse following initial therapy for multiple myeloma predicts poor outcomes in the era of novel agents. Leukemia. August 3, 2017. doi: 10.1038/leu.2016.147

3. Morè S, Offidani M, Corvatta L, et al. Belantamab mafodotin: from clinical trials data to real-life experiences. Cancers. May 27, 2023. doi: 10.3390/cancers15112948

4. A study to investigate the efficacy and safety of two doses of gsk2857916 in participants with multiple myeloma who have failed prior treatment with an anti-cd38 antibody. ClinicalTrials.gov Identifier: NCT03525678. Updated October 23, 2024. Accessed November 22, 2024. https://clinicaltrials.gov/study/NCT03525678

5. Study of single agent belantamab mafodotin versus pomalidomide plus low-dose dexamethasone (pom/​dex) in participants with relapsed/​refractory multiple myeloma (rrmm) (dreamm-3). ClinicalTrials.gov Identifier: NCT04162210. Updated June 10, 2024. Accessed November 22, 2024. https://clinicaltrials.gov/study/NCT04162210

6. GSK provides an update on blenrep (belantamab mafodotin-blmf) us marketing authorisation. GSK. November 22, 2022. Accessed November 22, 2024. https://www.gsk.com/en-gb/media/press-releases/gsk-provides-update-on-blenrep-us-marketing-authorisation/

7. Blenrep shows overall survival benefit in head-to-head dreamm-7 phase III trial for relapsed/refractory multiple myeloma. GSK. November 14, 2024. Accessed November 22, 2024. https://www.gsk.com/en-gb/media/press-releases/blenrep-shows-overall-survival-benefit-in-head-to-head-dreamm-7-phase-iii-trial-for-relapsedrefractory-multiple-myeloma/

8. Hungria V, Robak P, Hus M, et al. Belantamab mafodotin, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. June 1, 2024. doi: 10.1056/NEJMoa2405090