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Interim findings from the Phase III DREAMM-7 trial (NCT04246047) demonstrate that the combination of Blenrep (belantamab mafodotin) plus bortezomib and dexamethasone (BorDex) achieved the key secondary endpoint of significantly improved overall survival (OS) compared to the standard treatment of Darzalex (daratumumab) plus BorDex in patients with relapsed or refractory multiple myeloma (RRMM).1 These survival data from the interim analysis, along with safety results, will be presented at the 66th American Society of Hematology Annual Meeting and Exposition in December 2024.
“The overall survival results from the DREAMM-7 trial underscore the potential for this Blenrep combination to extend the lives of patients with relapsed/refractory multiple myeloma,” said Hesham Abdullah, senior vice president, global head oncology, R&D, GSK, in a press release. “This is a statistically significant and clinically meaningful advancement for patients and potentially transformative for treatment. We look forward to sharing these data with health authorities and presenting the full results at next month’s American Society of Hematology Annual Meeting.”1
The latest interim results follow data from the trial released earlier this year, also published by The New England Journal of Medicine (NEJM), showing the Blenrep combination produced a significant benefit in progression-free survival (PFS) compared to the Darzalex and BorDex combination in patients who experienced progression of multiple myeloma following prior administration of at least one line of therapy, which achieved the primary endpoint of the trial.2
Blenrep is a first-in-class, anti-B-cell maturation antigen (BCMA) therapy approved by the FDA on August 5, 2020, for adults with RRMM previously administered at least four therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. The drug’s antibody component is an afucosylated IgG1 directed against BCMA, a protein expressed on normal B lymphocytes and multiple myeloma cells.
After binding to BCMA, Blenrep is internalized, followed by release of MMAF via proteolytic cleavage, which disrupts the microtubule network and causes cell cycle arrest and death. Blenrep has demonstrated anti-tumor activity in multiple myeloma cells and mediated killing of tumor cells through MMAF-induced apoptosis, as well as by tumor cell lysis via antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.3
The multicenter, open-label, randomized DREAMM-7 trial is analyzing the efficacy and safety of Blenrep plus BorDex compared to the combination of Darzalex plus 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 in a 1:1 ratio to receive either the Blenrep combination or the Darzalex combination. Blenrep was administered at a dose of 2.5 mg/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, and minimal residual disease negativity rate as assessed by next-generation sequencing.
Investigators found that Blenrep plus BorDex produced a statistically significant and clinically meaningful reduction in the risk of death compared with Darzalex plus BorDex. Earlier data show patients administered the Blenrep combination achieved a statistically significant and clinically meaningful improvement in PFS, with a 59% reduction in the risk of disease progression or death compared with the Darzalex 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 Darzalex combination cohort.4
“The broad clinical benefit observed with [Blenrep plus BorDex] supports its potential integration into current treatment strategies used at the time of the first relapse or later,” the NEJM study authors wrote. “The PERSEUS trial recently showed a benefit of frontline treatment with daratumumab, bortezomib, lenalidomide, and dexamethasone. Once this frontline regimen is adopted, disease may become refractory to maintenance therapy with daratumumab and lenalidomide after frontline treatment, and new second-line regimens may be needed.”2
References
1. Blenrep shows overall survival benefit in head-to-head DREAMM-7 phase III trial for relapsed/refractory multiple myeloma. News release. GSK. November 14, 2024. Accessed November 14, 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/
2. Hungria V, et al. Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma. N Engl J Med 2024;391:393-407. DOI: 10.1056/NEJMoa2405090. Vol. 391 No. 5.
3. GSK provides update on DREAMM-3 phase III trial for Blenrep in relapsed/refractory multiple myeloma. GSK. November 7, 2022. Accessed November 14, 2024. https://www.gsk.com/en-gb/media/press-releases/gsk-provides-update-on-dreamm-3-phase-iii-trial-for-blenrep/
4. 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 November 14, 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/