GSK's Blenrep (belantamab mafodotin) in combination with bortezomib and dexamethasone (BorDex) has demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit in patients with relapsed or refractory multiple myeloma, according to results from the DREAMM-7 phase III trial. The trial compared the Blenrep combination to daratumumab plus BorDex, a standard of care, showing a significant reduction in the risk of death. These findings, presented at the American Society of Hematology Annual Meeting, suggest a potential paradigm shift in the treatment of multiple myeloma after first relapse.
DREAMM-7 Trial Details
The DREAMM-7 trial (NCT04246047) is a multicenter, open-label, randomized study evaluating the efficacy and safety of Blenrep plus BorDex versus Darzalex (daratumumab) plus BorDex in patients with relapsed or refractory multiple myeloma. The trial enrolled 494 participants who had previously received at least one line of therapy and experienced disease progression during or following their most recent treatment. Patients were randomized 1:1 to receive either the Blenrep combination (n=243) or the Darzalex combination (n=251).
Blenrep was administered intravenously at a dose of 2.5 mg/kg every three weeks. The primary endpoint was progression-free survival (PFS), while key secondary endpoints included OS, duration of response (DOR), minimal residual disease (MRD) negativity rate, overall response rate, safety, and quality of life outcomes.
Survival and Efficacy Results
At a median follow-up of 39.4 months, the Blenrep plus BorDex arm achieved a statistically significant 42% reduction in the risk of death compared to the Darzalex plus BorDex arm (HR 0.58; 95% CI: 0.43-0.79; p=0.00023). Median OS was not reached in either cohort; however, investigators estimated a median OS of 84 months in the Blenrep cohort compared to 51 months in the Darzalex cohort. The three-year OS rate was 74% in the Blenrep cohort and 60% in the Darzalex cohort.
In addition to the OS benefit, the Blenrep combination showed statistically significant superiority in MRD negativity and clinically meaningful improvements in DOR and PFS compared to the Darzalex combination.
Mechanism of Action and Prior Approvals
Blenrep is a first-in-class, anti-B-cell maturation antigen (BCMA) therapy. It was initially approved by the FDA in August 2020 for patients with relapsed or refractory multiple myeloma who had received at least four prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. The antibody component of Blenrep is an afucosylated IgG1 directed against BCMA, a protein expressed on normal B lymphocytes and multiple myeloma cells. Upon binding to BCMA, Blenrep is internalized, releasing MMAF via proteolytic cleavage, which disrupts the microtubule network, leading to cell cycle arrest and cell death.
Clinical Significance
"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. "This is a statistically significant and clinically meaningful advancement for patients and potentially transformative for treatment."
The DREAMM-7 data suggest that Blenrep in combination with BorDex could become a valuable option for patients with multiple myeloma who have relapsed or become refractory to initial treatment. These results may redefine the treatment landscape for this patient population, especially considering the increasing use of daratumumab-based regimens in the frontline setting.
