FDA approves BMS’ Abecma indication expansion for Multiple Myeloma
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Bristol Myers Squibb announced US FDA expanded Abecma’s indication on Apr. 4, 2024, making it available in earlier lines.
Indication:
Adult relapsed or refractory multiple myeloma after 2+ prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.
Abecma (idecabtagene vicleucel - ide-cel) was initially approved in March 2021 for multiple myeloma patients who have not responded to at least 4 prior lines of therapy.
The Mar. 15, 2024 FDA ODAC panel considered the risk acceptable and the Progression-Free Survival (PFS) benefit compelling. The cause of early deaths remained unclear. Some of the early death events occurred due to progressive disease, prior to Abecma treatment.
The approval comes almost 4 months after the Dec. 16, 2023 priority review deadline.
Clinical studies
Phase 3 MM-003 (KarMMa-3) is an open-label, global, randomized, and controlled trial. 254 patients were randomized to receive Abecma and 132 were randomized to receive standard regimens (2:1 ratio).
Most patients (85%) treated with Abecma received bridging therapy for control of their multiple myeloma during the manufacturing process.
The trial 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.
The primary efficacy measure was progression free survival (PFS) as determined by Independent Review Committee (IRC). Median PFS of Abecma arm was 13.3 months (95% CI: 11.8-16.1) vs. 4.4 months (95% CI: 3.4-5.9) for control (HR:0.49; 95% CI: 0.38-0.64; p<0.0001). The estimated median duration of follow-up at the primary PFS analysis was 15.9 months.
Overall response rate (ORR) for patients treated with Abecma was 71% vs. 42% for standard regimens.
The product label included warnings for early death, Cytokine Release Syndrome (CRS), neurologic toxicities, Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS), prolonged cytopenias, infections, hypogammaglobulinemia, hypersensitivity, and secondary malignancies.
· Early Death: A higher proportion of patients experienced death within 9 months after randomization in the Abecma arm (45/254; 18%) compared to the standard regimens arm (15/132; 11%) in KarMMa-3 trial. Early deaths occurred in 8% (20/254) and 0% prior to Abecma infusion and standard regimen administration, respectively, and 10% (25/254) and 11% (15/132) after Abecma infusion and standard regimen administration, respectively.
· Cytokine Release Syndrome (CRS): Among patients who received Abecma in the KarMMa and KarMMa-3 studies (n=349), any grade CRS occurred in 89% of patients, including Grade >3 CRS in 7% of patients, and 3 cases (0.9%) of Grade 5 CRS reported.
· Neurologic toxicities: Any grade neurotoxicity occurred in 40% of patients treated with Abecma in the KarMMa and KarMMa-3 studies, including Grade 3 neurotoxicity in 4% of patients, and 2 cases (0.6%) of Grade 4 neurotoxicity reported. At the safety update for KarMMa-3, 1 case of Grade 5 neurotoxicity was reported.
Link to product label Apr 2024
Link to previous FDA approval announcement Mar 2021