Belantamab Mafodotin Combo Improves PFS Vs SOC in R/R Multiple Myeloma

The safety and tolerability of belantamab mafodotin plus PomDex in the DREAMM-8 trial were comparable with prior reports of each individual agent.

Combining belantamab mafodotin-blmf (Blenrep) with pomalidomide (Pomalyst) and dexamethasone (PomDex) produced positive outcomes as second-line or later treatment among patients with relapsed/refractory multiple myeloma compared with bortezomib (Velcade) plus PomDex, according to topline results from the phase 3 DREAMM-8 trial (NCT04484623).¹

Treatment with belantamab mafodotin plus PomDex met the trial’s primary end point of progression-free survival (PFS) in a pre-specified interim analysis, which was unblinded following a recommendation from an independent data monitoring committee (IDMC). The experimental combination conferred a significant improvement in the time to death or disease progression compared with bortezomib plus PomDex.

The use of the belantamab mafodotin combination also resulted in a positive overall survival (OS) trend at the time of the analysis. Investigators will continue to follow up with patients for this end point.

The safety and tolerability of belantamab mafodotin plus PomDex in the DREAMM-8 trial were comparable with prior reports of each individual agent. Investigators plan to share detailed results from the trial at an upcoming medical conference and share their findings with regulatory health authorities.

“The results seen in both DREAMM-7 [NCT04246047] and DREAMM-8 provide strong clinical evidence of the robust efficacy shown with belantamab mafodotin in use with standard-of-care combinations. We now look forward to discussing these data with regulators,” Hesham Abdullah, senior vice president, and global head of Oncology Research & Development at GSK, the developers of belantamab mafodotin, said in the press release.¹

“If approved, we believe these combinations have the potential to redefine the treatment of relapsed or refractory multiple myeloma and advance the standard of care. This is exciting news for patients given the high unmet medical need for both efficacious and easily administered therapies with differing mechanisms of action,” he continued.

In the open-label, multicenter DREAMM-8 trial, 302 patients were randomly assigned 1:1 to receive belantamab mafodotin or bortezomib in combination with PomDex.

The trial’s primary end point was PFS based on International Myeloma Working Group (IMWG) criteria.² Secondary end points included duration of response, minimal residual disease negativity, OS, overall response rate, complete response rate, time to best response, time to progression, adverse effects, and health-related quality of life.

Patients 18 years and older with a confirmed diagnosis of multiple myeloma based on IMWG guidelines, an ECOG performance status of 0 to 2, and disease progression following at least 1 prior line of therapy including a lenalidomide (Revlimid)-containing regimen were able to enroll on the trial. Other eligibility criteria included having all prior treatment-related toxicities revert to less than or equal to grade 1 and adequate organ function.

Those who had active plasma cell leukemia, symptomatic amyloidosis or active polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, and skin changes at the time of screening were not eligible to enroll on the trial. Patients were also unsuitable for enrollment if they had prior allogeneic stem cell transplantation, plasmapheresis within 7 days of beginning study treatment, prior treatment with pomalidomide, evidence of cardiovascular risk, any major surgery within 4 weeks of entry, or evidence of active mucosal or internal bleeding.

Investigators previously presented findings from the phase 3 DREAMM-7 trial during an American Society of Clinical Oncology plenary session in February 2024.³ Findings highlighted a median PFS of 36.6 months (95% CI, 28.4-not reached [NR]) with belantamab mafodotin plus bortezomib and dexamethasone vs 13.4 months (95% CI, 11.1-17.5) among patients with relapsed/refractory multiple myeloma (HR, 0.41; 95% CI, 0.31-0.53; P <.00001).

References

1. GSK announces positive results from DREAMM-8 phase III trial for Blenrep versus standard of care combination in relapsed/refractory multiple myeloma. News release. GSK. March 7, 2024. Accessed March 7, 2024. https://tinyurl.com/29ntjyak
2. Belantamab mafodotin plus pomalidomide and dexamethasone (Pd) versus bortezomib plus Pd in relapsed/refractory multiple myeloma (DREAMM 8). ClinicalTrials.gov. Accessed March 7, 2024. https://tinyurl.com/ahnrn7dj
3. Mateos MV, Robak P, Hus M, et al. Results from the randomized phase III DREAMM-7 study of belantamab mafodotin (belamaf) + bortezomib, and dexamethasone (BVd) vs daratumumab, bortezomib, and dexamethasone (DVd) in relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2024;42(suppl 36):439572. doi:10.1200/JCO.2024.42.36_suppl.439572