Blenrep works better than Darzalex as early therapy, trial data show
Combo treatment may help slow progression of hard-to-treat multiple myeloma
When added to a second-line combination therapy, Blenrep (belantamab mafodotin) — developed by GlaxoSmithKline (GSK) for relapsed or treatment-resistant multiple myeloma — works better than Darzalex (daratumumab) at significantly delaying disease progression or death among patients.
That’s according to the results of a planned interim efficacy analysis of the global Phase 3 DREAMM-7 clinical trial (NCT04246047). These findings showed that treatment with Blenrep in people with relapsed or refractory, or hard-to-treat, myeloma (RRMM) met the primary goal of the study.
DREAMM-7, funded by GSK, is part of the company’s DREAMM — DRiving Excellence in Approaches to Multiple Myeloma — clinical development program to evaluate Blenrep. This particular study is assessing the effects of adding Blenrep versus Darzalex to a standard combination of Velcade (bortezomib) plus dexamethasone, or a BorDex combo.
“Patients with multiple myeloma need treatment options after first relapse that are efficacious, readily accessible and have novel mechanisms of action,” Hesham Abdullah, MD, the senior vice president and global head oncology of research and development at GSK, said in a company press release.
“We are particularly encouraged by the potential for [Blenrep] when combined with BorDex to address high unmet need in [RRMM], given the head-to-head comparison with the [Darzalex-based] standard of care regimen,” Abdullah added.
How Blenrep, Darzalex work to kill myeloma cancer cells
Blenrep is an antibody-based therapy approved in the U.S. and in Europe for adult RRMM patients who have received at least four previous lines of therapy. These may include a CD38 inhibitor, a proteasome inhibitor, and an immunomodulatory treatment.
It works by targeting the B-cell maturation antigen (BCMA) — a protein found at high levels on the surface of myeloma cells — and is modified to bind to a cancer-killing agent called auristatin F. Once the antibody binds to BCMA on the surface of cancer cells, auristatin F is released into the cells, promoting their death.
Janssen’s Darzalex is an antibody that blocks a protein called CD38 on the surface of myeloma cells, directly promoting cancer cell death and triggering immune responses against these cells.
It is approved in the U.S. to treat newly diagnosed myeloma patients, as well as RRMM patients, either alone or in combination with other approved treatments, such as the BorDex combo.
Time without disease progression studied in nearly 500 patients
The DREAMM-7 trial involved 494 RRMM patients who received at least one prior line of treatment, but among whom the disease continued to progress.
Participants were randomly assigned to receive either Blenrep or Darzalex on top of the standard Velcade plus dexamethasone combo. Blenrep was administered directly into the bloodstream every three weeks at a dose of 2.5 mg/kg.
The study’s main goal is to assess progression-free survival, or the time patients live without signs of disease progression, according to an independent data monitoring committee. Based on the positive findings in this measure, the committee recommended that the trial’s results be shared with the researchers and company earlier than initially expected.
Key secondary goals include overall survival, response duration, and the percentage of patients who are negative for minimal residual disease. This refers to the small number of cancer cells that may remain in a patient’s body after treatment and that can drive disease relapse and progression.
The safety and tolerability profiles of the Blenrep-BorDex combo were consistent with those reported for each individual medication. The interim DREAMM-7 results also support a “strong and clinically meaningful overall survival trend” favoring the Blenrep combo, GSK stated in the press release.
Trial participants will continue to be followed over time to assess overall survival.
The company plans to present these findings at a future scientific meeting and to discuss them with healthcare authorities.
In addition to this study, the larger DREAMM program is evaluating the clinical benefits of Blenrep as an early therapy, either alone or in combination with new and standard therapies, in multiple myeloma.
The program includes the DREAMM-2 study (NCT03525678), whose positive data supported Blenrep’s regulatory approvals for heavily-treated RRMM patients.
It also includes the DREAMM-8 trial (NCT04484623) that is testing Blenrep against Velcade, when combined with Pomalyst (pomalidomide) and dexamethasone, in RRMM patients who have received at least one prior line of treatment. This study may still be recruiting patients, and data are expected by 2024.
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