Phase III DREAMM-8 Trial Shows Efficacy of Blenrep Combo Over Standard of Care for Relapsed/Refractory Multiple Myeloma

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GSK’s Blenrep (belantamab mafodotin) combined with pomalidomide plus dexamethasone (PomDex) achieved the primary endpoint of progression-free survival (PFS) compared with standard of care bortezomib plus PomDex in the second-line and later treatment of relapsed or refractory multiple myeloma (RRMM) in the Phase III DREAMM-8 trial.¹ These data follow similar positive findings for Blenrep from the Phase III DREAMM-7 trial, in which the drug combined with bortezomib plus dexamethasone (BorDex) produced a significant improvement in median PFS in the second-line and later treatment of RRMM compared with standard of care combination therapy.²

“The results seen in both DREAMM-7 and DREAMM-8 provide strong clinical evidence of the robust efficacy shown with [Blenrep] in use with standard of care combinations. We now look forward to discussing these data with regulators,” Hesham Abdullah, GSK senior vice president, Global Head Oncology, R&D, said in a press release. “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.”¹

Blenrep is a first-in-class anti-BCMA therapy that was granted accelerated approval by the FDA in August 2020 for adult patients with RRMM previously administered at least four treatments that included an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. The antibody-drug conjugate has demonstrated antitumor activity in multiple myeloma cells as well as mediated killing of tumor cells via MMAF-induced apoptosis.³

The multicenter, open-label, randomized DREAMM-8 trial compared the efficacy and safety of Blenrep plus PomDex vs. the combination of bortezomib and PomDex in patients with RRMM previously administered at least one prior line of therapy for multiple myeloma, including a lenalidomide-containing regimen, and with documented disease progression during or following administration of their most recent therapy.

Investigators randomly assigned 302 patients at a 1:1 ratio to receive either Blenrep plus PomDex or bortezomib plus PomDex. In addition to the primary endpoint of PFS, secondary endpoints included overall survival (OS), overall response rate, duration of response, minimal residual disease negativity as assessed by next-generation sequencing, safety, and patient-reported and quality of life outcomes.

At a pre-specified interim analysis that was unblinded early based on a recommendation by an Independent Data Monitoring Committee, investigators found the Blenrep combination significantly improved the time to disease progression or death compared with bortezomib plus PomDex. Investigators reported a positive OS trend in favor of the Blenrep combination at the time of this analysis. The trial will continue to follow the trend in OS, according to GSK. In terms of safety, the tolerability of the Blenrep combination was broadly consistent with the known safety profile of the individual agents.

The DREAMM-7 trial evaluated the efficacy and safety of Blenrep with BorDex compared to the combination of daratumumab and BorDex. Patients administered the Blenrep combination showed a statistically significant and clinically meaningful improvement in PFS with a 59% drop in the risk of disease progression or death compared with the daratumumab plus BorDex combination. At a median follow-up of 28.2 months, median PFS was 36.6 months in the Blenrep combination cohort compared with 13.4 months in the daratumumab BorDex combination cohort.²

References

1. GSK announces positive results from DREAMM-8 phase III trial for Blenrep versus standard of care combination in relapsed/refractory multiple myeloma. GSK. News release. March 7, 2024. Accessed March 7, 2024. https://www.gsk.com/en-gb/media/press-releases/gsk-announces-positive-results-from-dreamm-8-phase-iii-trial-for-blenrep-versus-standard-of-care-combination-in-relapsedrefractory-multiple-myeloma/

2. DREAMM-7 phase III trial shows Blenrep combination nearly tripled median progression-free survival versus standard of care combination in patients with relapsed/refractory multiple myeloma. GSK. News release. February 5, 2024. Accessed March 7, 2024. https://www.gsk.com/en-gb/media/press-releases/dreamm-7-phase-iii-trial-shows-pfs-improvement-and-strong-os-trend-for-blenrep-combo-versus-soc-combo-in-multiple-myeloma/

3. Blenrep. Package insert. GlaxoSmithKline; 2020. Accessed March 7, 2024.