DREAMM-7 Trial Shows Blenrep's Potential to Transform Multiple Myeloma Treatment with Superior Survival

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Detailed results from an interim analysis of the Phase III DREAMM-7 trial (NCT04246047) demonstrated that Blenrep (belantamab mafodotin; GSK) combined with bortezomib and dexamethasone (BorDex) significantly improved overall survival (OS), progression-free survival (PFS), minimal residual disease (MRD) negativity rate, and duration of response (DOR) compared to Darzalex (daratumumab) plus BorDex in the second-line or later treatment of patients with relapsed or refractory multiple myeloma.^1,2 These data, presented at the 66th American Society of Hematology Annual Meeting and Exposition, could help to redefine the standard of care for this patient population, according to trial investigators.

“The totality of evidence from DREAMM-7 represents a potential paradigm shift for multiple myeloma patients who have experienced a relapse or become refractory to initial treatment,” DREAMM-7 principal investigator María-Victoria Mateos, MD, PhD, head of Myeloma and Clinical Trials Unit, Haematology Department and Professor of Medicine at the University of Salamanca, Spain, said in a press release. “The OS results shown with the belantamab mafodotin combination in DREAMM-7 further cement the potential of this regimen to prolong the lives of patients with relapsed or refractory multiple myeloma compared to a standard of care daratumumab combination.”¹

Blenrep is a first-in-class, anti-B-cell maturation antigen (BCMA) therapy approved by the FDA on August 5, 2020, for patients with relapsed or refractory multiple myeloma who received prior treatment with at least four therapies that included an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. Blenrep’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

Trial Design

DREAMM-7 is an ongoing, multicenter, open-label, randomized trial evaluating the efficacy and safety of Blenrep plus BorDex compared to the combination of Darzalex plus BorDex in patients with relapsed or refractory multiple myeloma previously treated with at least one line of therapy for multiple myeloma and who experienced documented disease progression during or following administration of their most recent therapy. The trial’s primary endpoint is PFS per independent review committee, with key secondary endpoints that included OS, DOR, MRD negativity rate as assessed by next-generation sequencing, overall response rate, safety, and quality of life outcomes.

Investigators randomly assigned 494 participants in a 1:1 ratio to receive either the Blenrep combination (n=243) or the Darzalex combination (n=251). Blenrep was administered at a dose of 2.5 mg/kg intravenously every three weeks.

Results

At a median follow up of 39.4 months, Blenrep plus BorDex achieved a statistically significant 42% decrease in the risk of death compared to Darzalex plus BorDex (HR 0.58; 95% CI: 0.43-0.79; p=0.00023). Median OS was not reached in either treatment cohort, but investigators estimated a median OS of 84 months for the Blenrep cohort compared with 51 months in the Darzalex cohort. Three-year OS was 74% in the Blenrep cohort compared to 60% in the Darzalex cohort. This survival benefit with Blenrep was observed as early as four months into treatment and continued over time, according to the investigators.

Blenrep plus BorDex also showed statistically significant superiority in MRD negativity, with a greater than 2.5-fold improvement at the time of the primary analysis. Blenrep plus BorDex also achieved clinically meaningful improvements in DOR and PFS compared to Darzalex plus BorDex, which indicates a deeper and more durable response, according to investigators.

“The compelling overall survival data from the DREAMM-7 trial establish the potential of Blenrep in combination to significantly extend the lives of patients with multiple myeloma at or after first relapse,” Hesham Abdullah, senior vice president, global head Oncology, R&D, GSK, said in the release. “This represents an important advancement that could redefine the treatment of relapsed or refractory multiple myeloma.”¹

References

1. Blenrep shows significant overall survival benefit, reducing the risk of death by 42% in multiple myeloma at or after first relapse. News release. GSK. December 9, 2024. Accessed December 16, 2024. https://www.gsk.com/en-gb/media/press-releases/blenrep-shows-significant-overall-survival-benefit-reducing-the-risk-of-death-by-42-in-multiple-myeloma-at-or-after-first-relapse/

2. 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. October 14, 2024. Accessed December 16, 2024. https://clinicaltrials.gov/study/NCT04246047

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/