Blenrep-Based Regimen Yields PFS Benefit in Relapsed/Refractory Myeloma

CHICAGO — Progression-free survival (PFS) was significantly higher with belantamab mafodotin (belamaf; Blenrep) combined with pomalidomide (Pomalyst) and dexamethasone (BPd), compared with standard-of-care pomalidomide, bortezomib (Velcade), and dexamethasone (PVd) in patients with relapsed/refractory multiple myeloma, according to results from the phase III DREAMM-8 trial presented here.

At a median follow-up of 21.8 months, the 12-month estimated PFS rates were 71% with BPd versus 51% with PVd, translating into a 48% reduced risk of disease progression or death with the investigational triplet (HR 0.52, 95% CI 0.37-0.73, P<0.001). Median PFS was not reached with BPd compared with 12.7 months with PVd, reported Suzanne Trudel, MD, of the Princess Margaret Cancer Center in Toronto, at the annual meeting of the American Society of Clinical Oncology (ASCO).

Ocular adverse events in the belantamab mafodotin group — of particular interest with the B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate — were reversible with appropriate dose modifications and marked by low discontinuation rates, Trudel added.

The study was also published in the New England Journal of Medicine.

“Taken together with the results of DREAMM-7 … these data highlight the potential of belamaf-containing triplets to address an unmet need of novel regimens to treat patients with myeloma for first relapse,” she said during a press briefing.

In the DREAMM-7 trial, patients who received belantamab mafodotin in combination with bortezomib and dexamethasone as a second-line treatment for relapsed or refractory disease had significantly greater median PFS compared with patients who received daratumumab (Darzalex) plus bortezomib and dexamethasone.

The results from the two trials represents a second chance for a drug that was originally granted accelerated approval by the FDA in 2020 for the treatment of adults with relapsed or refractory multiple myeloma that failed a minimum of four prior agents.

However, after the DREAMM-3 confirmatory trial failed to meet the primary endpoint of PFS, the FDA requested that GSK, the agent’s developer, withdraw belantamab mafodotin from the market.

When asked whether the message from the results of the DREAMM-7 and DREAMM-8 studies is that belantamab mafodotin should be returned to the market — at least in an earlier line setting — Trudel said that antibody drug conjugates “are a difficult group of drugs to develop because of the toxicities you see. But we’ve learned from antibody drug conjugates in [acute myeloid leukemia] you have to play around and figure out how to dose modify and to reduce the toxicities, and I think we’re getting that point across with belamaf now that it is more manageable.”

“It’s unfortunate that DREAMM-3 was negative,” she said. “But clearly … DREAMM-7 and DREAMM-8 show the utility of this drug in early relapse.”

ASCO discussant Oreofe Odejide, MD, MPH, of the Dana-Farber Cancer Institute in Boston, pointed out that the development of triplet and quadruplet regimens to treat multiple myeloma in the first line, while improving outcomes, “also means that when patients relapse, they’ve often been exposed and may not respond as well to many anti-myeloma treatments.”

“So, there is an unmet need for novel combination therapies in the relapse setting. And belantamab mafodotin, based on these findings, is meeting that need,” she continued. “Belantamab plus pomalidomide and dexamethasone is poised to be a new treatment option — potentially — for patients who have relapsed or refractory myeloma.”

DREAMM-8 included 302 patients at 95 sites in 18 countries randomized to BPd or PVd. Median age was around 67, more than half were men, and over 85% were white. Patient characteristics at baseline were similar in both groups, with two exceptions — the percentage of patients who were ages 75 years or older was higher in the PVd group, and the percentage of patients with baseline extramedullary disease was higher in the BPd group.

Overall, 53% of patients had received one previous line of therapy, and 14% had received four or more previous lines. All patients had previously received lenalidomide, and 78% had lenalidomide-refractory disease.

The overall response rate was 77% for those receiving BPd compared to 72% for those receiving PVd. Additionally, 40% of patients treated with BPd achieved a complete response or better compared to 16% of patients who were treated with PVd.

The median duration of response was not yet reached in those who received BPd, and was 17.5 months in those who received PVd.

Data for overall survival were immature at the current interim analysis, although Trudel noted there was an early trend of an OS benefit with 12-month OS of 83% with BPd and 76% with PVd (HR 0.77, 95% CI 0.53-1.14).

“The overall survival benefit came despite the use of effective anti-myeloma therapies, including anti-BCMA targeted therapy and anti-CD38 for patients who progressed on the PVd arm,” Trudel observed.

Regarding safety, Trudel reported that more patients had grade 3 or higher adverse events (AEs) in the BPd arm (94% vs 76%) as well as more serious AEs (63% vs 45%), but that when adjusted for time on treatment, these AEs were actually similar or even lower in the BPd arm. AEs leading to dose reductions or permanent discontinuations were similar in the two arms.

“Ocular events were managed with dose delays and modifications,” Trudel noted. “These protocol pre-specified dose modifications led to a low discontinuation rate for ocular adverse events of 9%.”

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