Interim Analysis of DREAMM-7 Phase III Trial Shows Significant Survival Benefit With Blenrep in Multiple Myeloma

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Data from an interim analysis of the Phase III DREAMM-7 trial (NCT04246047) show that treatment with GSK’s Blenrep (belantamab mafodotin) combined with bortezomib plus dexamethasone (BorDex) produced a significant improvement to median progression-free survival (PFS) in the second-line and later treatment of relapsed or refractory multiple myeloma (RRMM) compared with standard of care combination therapy.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.²

“The substantial (PFS) benefit and strong overall survival (OS) trend compared to a daratumumab standard of care combination reinforce our belief in the potential for belantamab mafodotin used in combination to redefine the treatment of multiple myeloma at or after first relapse,” said Hesham Abdullah, senior vice president, Global Head Oncology, R&D, GSK, in a press release. “We plan on sharing these results with health authorities worldwide.”¹

Blenrep is an antibody-drug conjugate that has demonstrated antitumor activity in multiple myeloma cells as well as mediated killing of tumor cells via MMAF-induced apoptosis.²

The multicenter, open-label, randomized DREAMM-7 trial is analyzing the efficacy and safety of Blenrep with BorDex compared to the combination of daratumumab and BorDex in patients with RRMM previously administered at least one line of therapy for multiple myeloma and who experienced documented disease progression during or following administration of the most recent treatment.

Investigators randomly assigned 494 participants 1:1 to either the Blenrep combination cohort or the daratumumab and BorDex combination cohort. Blenrep is set to be administered at a dose of 2.5mg/kg intravenously every three weeks. The trial’s primary endpoint is PFS as per an independent review committee, with key secondary endpoints that include OS, duration of response (DOR), and minimal residual disease (MRD) negativity rate as assessed by next-generation sequencing.

Patients in the Blenrep treatment group 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 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.

Further, the Blenrep combination cohort showed clinically meaningful improvements across the trial’s secondary efficacy endpoints, which included MRD negativity rate and median DOR. At the time of the interim analysis, the Blenrep combination produced a clinically meaningful OS trend with a 43% decrease in the risk of death; however, the combination has yet to achieve the interim criteria for OS statistical significance, with further analyses planned.

In terms of safety, the adverse event profile in the Blenrep combination cohort was consistent with what has previously been reported for the individual agents.

“These results from DREAMM-7 show how belantamab mafodotin in combination with BorDex represents a significant improvement over the daratumumab-based regimen in a second-line multiple myeloma treatment setting,” said DREAMM-7 principal investigator María-Victoria Mateos, MD, PhD, head of Myeloma and Clinical Trials Unit, Hematology Department and professor of Medicine at the University of Salamanca, Spain, in a press release. “Anti-BCMA therapies are helping to improve outcomes for patients with multiple myeloma, and having an off-the-shelf option, like belantamab mafodotin, that can be administered in a community oncology treatment center where the majority of patients are treated has the potential to transform the way we treat myeloma at or after first relapse.”¹

References

1. 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 February 6, 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/

2. Blenrep. Package insert. GlaxoSmithKline; 2020. Accessed February 6, 2024.