Blenrep lowers risk of disease progression vs. bortezomib in trial

Relapsed patients responded to treatment, data show

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Two hands, a stethoscope and a handful of pills surround a graph showing positively trending data from a clinical trial.

GSK‘s Blenrep (belantamab mafodotin) cut the risk of cancer progression nearly in half compared with bortezomib when used in combination with other therapies to treat multiple myeloma patients who’d had at least one previous disease relapse.

The benefits of Blenrep, used in combination with Pomalyst (pomalidomide) and dexamethasone (PomDex), were observed across key patient subgroups, including those considered to have a poor prognosis.

The data from the Phase 3 DREAMM-8 clinical trial (NCT04484623) are the second set of trial results to show that Blenrep is favorable to other standard-of-care combinations as soon as after the first myeloma relapse. In the DREAMM-7 clinical trial (NCT04246047), Blenrep was superior to Darzalex (daratumumab) for slowing disease progression when used with bortezomib and dexamethasone.

Interim DREAMM-8 findings were presented at a recent scientific conference and simultaneously published in The New England Journal of Medicine. The GSK-funded study was titled, “Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma.

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‘Exciting news’

“With the robust results from the DREAMM-8 … trial, we now have consistent data from two phase III trials supporting the potential for Blenrep combinations to redefine the treatment of multiple myeloma at or after first relapse,” Hesham Abdullah, senior vice president and global head of oncology, research and development at GSK, said in a company press release. “This is exciting news given the high unmet need for new and efficacious combinations once patients relapse or stop responding to initial treatments. We continue to share data and discuss our path forward with regulators.”

Blenrep contains an antibody targeted against the BCMA protein found on myeloma cells, linked to a substance that’s toxic to cells (cytotoxic) called auristatin F. Essentially, the antibody helps target auristatin F specifically to cancer cells, where it works to kill them off.

It is approved in the U.S. and Europe for multiple myeloma patients who have received four or more prior lines of treatment, but GSK is still conducting studies to evaluate its potential as part of earlier lines of treatment.

DREAMM-8 enrolled 302 patients with relapsed/refractory myeloma who had been previously treated with at least one line of therapy, including lenalidomide (sold as Revlimid, with generics available), and who showed signs of disease progression on their most recent treatment.

Participants were randomly assigned to receive Blenrep or bortezomib along with PomDex. Bortezomib (sold as Velcade and generics) is approved for treating multiple myeloma and mantle cell lymphoma in the U.S. and is commonly combined with other standard myeloma treatments in clinical practice.

The study’s main goal was to evaluate survival time without signs of cancer progression.

Results showed that the Blenrep combination lowered the risk of cancer progression or death by nearly 50% relative to the standard of care combination — a statistically significant and clinically meaningful difference.

With a median follow-up of 21.8 months, the median progression-free survival time hadn’t yet been reached in the Blenrep group, meaning not enough patients had reached those outcomes to calculate the average. In the standard care group, the median progression-free survival time was a little over a year.

Estimated one-year progression-free survival was 71% with Blenrep, vs. 51% with bortezomib.

Blenrep’s benefits were observed even in patients deemed to have poor prognosis due to a failure to respond to lenalidomide or with certain high-risk cellular features.

While data related to overall survival similarly favored Blenrep, the difference was not statistically significant. More long-term follow-up data are needed before conclusions can be drawn, the researchers said.

More patients on the experimental combination were considered treatment responders — those seeing at least a partial response to therapy — compared with standard care (77% vs. 72%), and a higher proportion achieved a complete response or better (40% vs. 16%).

Among treatment responders, the median response duration was 17.5 months with standard care, while the median hadn’t yet been reached with Blenrep.

The safety of the Blenrep combination regimen was consistent with the known side effect profile of the individual medications. As expected, eye-related side effects were common with Blenrep, occurring in 89% of participants, but were generally reversible and manageable with dose alterations.

“This regimen could become an important treatment option for patients with multiple myeloma at first relapse and for subsequent relapses,” Suzanne Trudel, MD, multiple myeloma specialist at the Princess Margaret Cancer Centre in Toronto and the study’s senior author, said in a separate press release from the American Society of Clinical Oncology.  “It is suitable for a broad range of patients and can be given in a community oncology setting without the need for specialized cancer center support,” Trudel said.

Follow-up in DREAMM-8 is ongoing to further assess treatment effects on overall survival.