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SAN DIEGO -- A significant overall survival (OS) benefit with belantamab mafodotin (belantamab; Blenrep) in a phase III trial of relapsed or refractory multiple myeloma should smooth the way for the drug's reintroduction to the U.S. market.

In the DREAMM-7 study, OS rates at 3 years improved from 60% with the three-drug regimen of daratumumab (Darzalex), bortezomib (Velcade), and dexamethasone (DVd) to 74% with belantamab, bortezomib, and dexamethasone (BVd; HR 0.58, 95% CI 0.43-0.79, P=0.0023), reported Vania Hungria, MD, PhD, of Clinica São Germano in São Paulo, Brazil.

Modeling data predicted a nearly 3-year improvement in median OS, from 51 months with DVd to 84 months with the belantamab-based regimen, according to findings presented at the American Society of Hematology annual meeting here.

"These results further support the use of BVd as a potential new standard of care in relapsed or refractory multiple myeloma," said Hungria, adding that the benefit was maintained after subsequent anti-myeloma therapy. Safety was consistent with the , she said.

As has been previously reported, the belantamab-based regimen prolonged progression-free survival (PFS) by nearly 2 years in the trial, meeting its primary endpoint. The monoclonal antibody, which targets B-cell maturation antigen (BCMA), also led to improvements in a host of other oncologic outcomes.

The FDA in 2020 granted accelerated approval to belantamab for relapsed or refractory multiple myeloma. However, after a confirmatory trial failed to meet its primary endpoint of PFS, the drug's developer in 2022 announced plans to the drug from the U.S. market.

Now, with the DREAMM-7 findings and positive data from another randomized trial, the anti-BCMA drug appears poised to regain its approval status.

Blenrep Would Rejoin Crowded Anti-BCMA Field

Reached for comment on the new study results, Sarah Holstein, MD, PhD, of the University of Nebraska Medical Center in Omaha, said "it is clear that in early lines of therapy, belantamab is superior to daratumumab, which is an important finding." But she added caveats.

"One, we are now in an era where patients are routinely receiving daratumumab in the upfront setting. Two, almost none of the patients enrolled in this study had access to BCMA therapy at subsequent lines of therapy," said Holstein, who was not involved in the research. "If you are living in an area of the world where you have access to other types of BCMA-directed therapy, then the significance of this study dims."

Two anti-BCMA CAR T-cell therapies are already available for myeloma -- ciltacabtagene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (Abecma) -- and the FDA recently expanded their approvals to include earlier lines of treatment. Cilta-cel showed an OS benefit as a second-line therapy in CARTITUDE-4.

"The key question here is whether one would choose belantamab or CAR-T first, which of course is not answered by the DREAMM-7 trial," Holstein told 名媛直播 via email. "If belantamab is reintroduced, I view it as an option to consider as potential salvage post-CAR-T or post-bispecific antibody therapy. In addition, for patients who for whatever reason are not CAR-T-eligible (or choose not to pursue CAR-T), then it would be a reasonable alternative."

Sequencing of BCMA-directed therapies matters, added Holstein, noting that findings from along with real-world data suggest that patients have an inferior response to BCMA-directed CAR T-cell therapy if they have already received another anti-BCMA agent.

"There is also the issue of toxicities, and for some patients, assuming that they have other options (e.g., CAR-T), having ongoing visual acuity issues that interfere with activities such as reading and driving would be an important reason to pursue a non-belantamab option," she said.

During her presentation, Hungria spent some time discussing the ocular adverse events (AEs) associated with belantamab. Overall, about a third of patients had a clinically meaningful drop in best corrected visual acuity and 10% discontinued treatment due to an ocular AE; blurred vision was the most common event, with a handful of patients' vision worsening to 20/200 during the trial.

However, despite longer dosing intervals for patients with ocular AEs, response rates remained high and most of the events resolved with the dose modifications, Hungria said.

Study Details

randomized 494 patients with relapsed or refractory multiple myeloma 1:1 to either BVd or DVd. Participants received the three-drug regimens for eight cycles followed by monotherapy with either belantamab or daratumumab, respectively. Patients were excluded if they had already received an anti-BCMA agent, and they could not have disease refractory to daratumumab or bortezomib. Median follow-up for the analysis was 39.4 months.

Participants had a median age of about 65, a majority were men, and upwards of 80% were white. About 40% had stage I disease on the Revised Multiple Myeloma International Staging System (R-ISS) and over 50% had R-ISS stage II disease; more than a fourth had high-risk cytogenetic abnormalities as well.

Approximately 50% had received only one prior line of therapy, while 36-39% had received two or three and 11-12% received four or more prior lines. Over 80% had been exposed to an immunomodulatory drug, with about one-third refractory to lenalidomide (Revlimid), while just 1-2% had already received daratumumab.

Along with the improved survival outcomes, BVd led to higher overall response rates (83% vs 71%) and doubled the number of complete responses (36% vs 18%) and the duration of response (40.8 vs 17.8 months). The proportion achieving minimal residual disease negativity also increased significantly with the belantamab regimen.

Among patients receiving subsequent treatment in the BVd arm, the most common next line of therapy included a CD38-directed antibody such as daratumumab or isatuximab (Sarclisa).

The belantamab-based regimen was associated with more grade 3/4 AEs (95% vs 78% with DVd) and serious AEs (53% vs 38%), as well as more AEs that led to drug discontinuation (28% vs 15%) or dose reductions (75% vs 59%). Non-ocular grade ≥3 AEs of clinical interest for BVd versus DVd included thrombocytopenia (56% vs 35%, respectively), anemia (9% vs 10%), neutropenia (14% vs 10%), and pneumonia (12% vs 4%).

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