Blenrep delays disease progression by nearly 3X versus Darzalex

Findings were from a two-year interim analysis of Phase 3 DREAMM-7 trial

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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GlaxoSmithKline (GSK)’s Blenrep (belantamab mafodotin) significantly reduced by more than half the risk of disease progression or death in people with relapsed or refractory multiple myeloma (RRMM) relative to Darzalex (daratumumab).

A nearly three times greater delay in disease progression and a 43% lower risk of death was associated with Blenrep-treated patients over those on Darzalex, according to a two-year interim analysis of the global Phase 3 DREAMM-7 clinical trial (NCT04246047) that’s testing Blenrep versus Darzalex when added to a standard combination of Velcade (bortezomib) plus dexamethasone, or a BorDex combo.

GSK had announced a planned interim analysis that showed the trial met its main goal of showing Blenrep was superior to Darzalex at extending time to disease progression or death, but no details were provided at the time.

Here, detailed results were presented by María-Victoria Mateos, MD, PhD, the trial’s principal investigator at the University of Salamanca, Spain, at the American Society of Clinical Oncology (ASCO) Plenary Series on Feb. 6. The oral presentation was titled “Results from the randomized phase III DREAMM-7 study of belantamab mafodotin (belamaf) + bortezomib, and dexamethasone (BVd) vs daratumumab, bortezomib, and dexamethasone (DVd) in relapsed/refractory multiple myeloma (RRMM).”

“The substantial progression-free survival benefit and strong overall survival trend compared to a [Darzalex] standard of care combination reinforce our belief in the potential for [Blenrep] used in combination to redefine the treatment of multiple myeloma at or after first relapse,” Hesham Abdullah, MD, GSK’s senior vice president and global head oncology of research and development, said in a company press release. “We plan on sharing these results with health authorities worldwide.”

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Longer survival, progression delay with Blenrep

Blenrep is approved in the U.S. and Europe for adult RRMM patients who’ve received four or more lines of treatment, including a CD38 inhibitor, a proteasome inhibitor, and an immunomodulatory treatment.

The antibody-therapy targets a protein, called B-cell maturation antigen (BCMA), that’s present at high levels on the surface of myeloma cells. After binding, it releases auristatin F, a cancer-killing agent, triggering the cells’ death.

Darzalex, marketed by Janssen, is approved in the U.S. for newly diagnosed myeloma patients, along with RRMM patients, either alone or with other approved treatments, including the BorDex combo. An antibody-based therapy, it blocks the CD38 protein at the surface of myeloma cells, promoting their death both directly and indirectly by triggering immune responses against them.

In the DREAMM-7 trial, 494 RRMM patients given a minimum of one previous therapy line they failed to respond to were randomly assigned to either Blenrep (243 patients) or Darzalex (251 patients) in addition the standard BorDex combo.

Newly presented data, at a median follow-up of little over two years, showed those treated with the Blenrep-BorDex combo lived for a median of 36.6 months (about three years) without signs of disease progression compared with 13.4 months (about a year) with the Darzalex-BorDex combo. This reflected a nearly two-year difference in progression-free survival and a 59% reduction in the risk of disease progression or death with Blenrep, meeting the trial’s main goal.

Blenrep’s superiority was observed across all prespecified patient groups, including those who failed to respond to the immunomodulatory therapy lenalidomide (sold as Revlimid, with generics available) and patients with high-risk chromosome abnormalities.

Blenrep meets other efficacy goals

The Blenrep-BorDex combo also resulted in clinically meaningful improvements across all secondary efficacy goals. These included a twofold longer treatment response (median, 35.6 vs. 17.8 months) and a nearly twofold higher proportion of patients achieving a complete response, or the disappearance of all cancer signs (20.6% vs. 12%).

A higher proportion of Blenrep-treated patients also were negative for minimal residual disease, or the small number of myeloma cells that may remain after treatment and cause a relapse (24.7% vs. 9.6%).

The Blenrep-BorDex combo also led to a clinically meaningful longer overall survival, with patients on the therapy having a 43% reduction in the risk of death relative to those on the Darzalex-BorDex combo. This difference hasn’t reached the interim criteria for statistical significance, but patients continue to be followed.

The safety and tolerability profile of the Blenrep-BorDex combo were consistent with those reported for each individual medication.

No significant group differences were detected regarding health-related quality of life, as assessed with the EORTC Core Quality of Life questionnaire.

The Blenrep combo was associated with higher rates of serious or life-threatening non-eye-related events, including low platelet counts (55% vs. 35%), low counts of a type of immune cells called neutrophils (12% vs. 6%), pneumonia (12% vs. 4%) and low counts of red blood cells (8% vs. 10%).

Eye-related side effects, which are associated with Blenrep, occurred in 34% of these patients, and included blurred vision (22%), dry eyes (7%), eye irritation (5%), and visual impairment (5%). The symptoms were generally reversible and managed by dose reductions, and only led to it being discontinued in 9% of cases.

“These results from DREAMM-7 show how [Blenrep] in combination with BorDex represents a significant improvement over the [Darzalex-based] regimen in a second-line multiple myeloma treatment setting,” Mateos said. “Anti-BCMA therapies are helping to improve outcomes for patients with multiple myeloma, and having an off-the-shelf option, like [Blenrep], 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.”