12 August 2022 - - US-based pharmaceutical company Bristol Myers Squibb (NYSE: BMY) and 2seventy bio, Inc. (NASDAQ: TSVT) have released positive topline results from KarMMa-3, a Phase 3, global, randomized, multicenter, open-label study evaluating Abecma (idecabtagene vicleucel) compared to standard combination regimens in adults with multiple myeloma that is relapsed and refractory after two to four prior lines of therapy and refractory to the last regimen, the companies said.

KarMMa-3 is the first randomized clinical trial to evaluate a CAR T cell therapy in multiple myeloma.

Results of a pre-specified interim analysis conducted through an independent review committee showed that KarMMa-3 met its primary endpoint of demonstrating a statistically significant improvement in progression-free survival.

Treatment with Abecma also showed an improvement in the key secondary endpoint of overall response rate compared to standard regimens.

Follow-up for overall survival, a key secondary endpoint, remains ongoing.

Safety results in the trial were consistent with the well-established and predictable safety profile of Abecma previously demonstrated in the pivotal KarMMa trial. No new safety signals were reported in this study, the companies said.

Bristol Myers Squibb and 2seventy bio will complete a full evaluation of the KarMMa-3 data and work with investigators to present detailed results at an upcoming medical meeting, as well as discuss these results with health authorities.

The companies thank the patients and investigators who are participating in the KarMMa-3 clinical trial.

Abecma was approved by the US Food and Drug Administration in March 2021 for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.

Abecma is also approved in the European Union, Switzerland, Japan, Canada and the United Kingdom for adult patients with relapsed or refractory multiple myeloma who have received at least three prior therapies.

KarMMa-3 (NCT03651128) is a pivotal, Phase 3, global, randomized, multicenter trial evaluating Abecma compared to standard regimens in patients with multiple myeloma that is relapsed and refractory after two to four prior lines of treatment and refractory to the last treatment regimen.

Patients were randomized to receive Abecma or standard regimens that consisted of combinations that included daratumumab, pomalidomide, dexamethasone, bortezomib, ixazomib, lenalidomide, carfilzomib or elotuzumab.

The primary endpoint evaluated in this study is progression-free survival, defined as time from randomization to the first documentation of progressive disease or death due to any cause, whichever occurs first.

Key secondary endpoints include overall response rate and overall survival.

Abecma is the first-in-class B-cell maturation antigen -directed chimeric antigen receptor T cell immunotherapy approved in the US for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. 

Abecma recognizes and binds to BCMA on the surface of multiple myeloma cells leading to CAR T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells. 

Abecma is being jointly developed and commercialized in the US as part of a Co-Development, Co-Promotion, and Profit Share Agreement between Bristol Myers Squibb and 2seventy bio.

The companies' clinical development program for Abecma includes clinical studies (KarMMa-2, KarMMa-3, KarMMa-7) in earlier lines of treatment for patients with multiple myeloma.