Bristol-Myers Squibb Company and 2seventy bio, Inc. have announced that on April 4, 2024, the U.S. Food and Drug Administration (FDA) approved Abecma®(idecabtagene vicleucel; ide-cel) for the treatment of adult patients with relapsed or refractory multiple myeloma after two or more prior lines of therapy including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody, based on results from the KarMMa-3 trial. This approval expands Abecma?s indication, making it available in earlier lines to patients who have relapsed or become refractory after exposure to these three main classes of treatment (triple-class exposed), after two prior lines of therapy. Abecma is administered as a one-time infusion, with a new recommended dose range of 300 to 510 x 106 CAR-positive T cells.

Please see the Important Safety Information section below, including Boxed WARNINGS for Abecma regarding Cytokine Release Syndrome, Neurologic Toxicities, Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome, Prolonged Cytopenia, and Secondary Hematological Malignancies. Despite advances in treatment, multiple myeloma remains an incurable disease characterized by periods of remission and relapse. In early lines of treatment, regimens consisting of combinations of IMiDs, PIs, and anti-CD38 monoclonal antibodies are often used to help manage the disease.

Unfortunately, as many patients go on to relapse and/or become refractory to these classes of therapy, more patients are becoming triple-class exposed earlier in their treatment journey. There are limited options for these patients, and triple-class exposed relapsed and/or refractory multiple myeloma is associated with poor outcomes and a median progression-free survival (PFS) of three to five months. In this patient population with high unmet need, Abecma has demonstrated clinically meaningful and statistically significant improvements in PFS (95% CI: 13.3 months vs.

4.4 months [HR: 0.49; p<0.0001]). In addition, Abecma exhibited a well-established safety profile with mostly low-grade cytokine release syndrome and neurotoxicity. No cases of Parkinsonism were reported in the study.

To support this approval and future expansions, Bristol Myers Squibb has made continuous investments to increase manufacturing capacity and has shown a consistently high manufacturing success rate of 94% for Abecma in the commercial setting. Abecma was recently approved in Japan, Switzerland and the European Union for adult patients with triple-class exposed relapsed and/or refractory multiple myeloma after two prior lines of therapy, making it the only CAR T cell therapy available globally for earlier lines of therapy for patients with triple-class exposed relapsed and/or refractory multiple myeloma. Abecma is also currently approved in Great Britain and Israel for adult patients with triple-class exposed relapsed and refractory multiple myeloma after three or more prior lines of therapy.

The KarMMa-3 trial is a pivotal, Phase 3, open-label, global, randomized, controlled trial evaluating Abecma compared to standard regimens in patients with relapsed and refractory multiple myeloma who have received two to four prior lines of treatment, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody, and were refractory to the last treatment regimen, with 94% of patients with disease refractory to prior treatment with daratumumab. KarMMa-3 is the only Phase 3 trial to evaluate a CAR T cell therapy in a patient population consisting entirely of triple-class exposed relapsed and refractory multiple myeloma patients. The trial?s patient-centric design allowed for crossover from standard regimens to Abecma upon confirmed disease progression.

At the time of the final progression-free survival (PFS) analysis, more than half (56%) of patients in the standard regimens arm crossed over to receive Abecma as a subsequent therapy. In the study, 254 patients were randomized to receive Abecma and 132 were randomized to receive standard regimens that consisted of combinations that included daratumumab, pomalidomide, and dexamethasone (DPd), daratumumab, bortezomib, and dexamethasone (DVd), ixazomib, lenalidomide, and dexamethasone (IRd), carfilzomib and dexamethasone (Kd) or elotuzumab, pomalidomide and dexamethasone (EPd) chosen based on their most recent treatment regimen and investigator discretion. In the Abecma arm, pretreatment consisted of leukapheresis and optional bridging therapy.

The choice to use bridging therapy was at the discretion of the investigator.