Abecma (idecabtagene vicleucel)

P2, N=78, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

Finally, validating functional relevance, pharmacologic inhibition of NF-κB abrogated CAR-T cytotoxicity and cytokine production in vitro. Our results support that NFKB in the ide-cel product marks a signaling axis impacting CAR-T function and NFKB activity represents a global marker of T cell fitness present prior to CAR-T manufacture.

Bone marrow samples were treated ex vivo with BCMA CAR T cells, TCEs (elranatamab, SAR442257), or activated T cells, and analyzed by flow cytometry. CD45 upregulation was validated in patient samples before and after idecabtagene vicleucel therapy (anti-BCMA CAR T-cell therapy), and by using in an in vivo mouse model of disseminated MM...Mechanistic studies implicated secreted HSP70, while bulk RNA-sequencing revealed increased LAG-3, IFN-γ signaling, and PD-L1 expression. These findings suggest T cell-redirecting therapy (TCRT) drives an immuno-evasive phenotype defined by CD45 upregulation and immune checkpoint activation, supporting combination strategies of TCRT with checkpoint inhibitors to overcome resistance in relapsed/refractory MM.

These findings provide a signal supporting the feasibility and safety of bendamustine-based lymphodepletion and highlight the prognostic relevance of renal function in Cilta-Cel-treated patients. While Cilta-Cel generally confers superior efficacy compared with Ide-Cel, this advantage may be attenuated in patients with moderate/severe CKD, potentially due to competing risks such as frailty, early toxicity, or impaired cellular fitness.

Wearable devices are feasible for early CRS detection and may support outpatient CAR-T care. Larger outpatient studies are warranted.

P1, N=15, Recruiting, City of Hope Medical Center | Trial completion date: Mar 2026 --> Sep 2026 | Trial primary completion date: Mar 2026 --> Sep 2026

P2, N=24, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

Two patients who had relapsed after CAR T-cell treatment with idecabtagene vicleucel achieved partial and very good partial responses and were successfully transitioned to a second CAR T-cell therapy with ciltacabtagene autoleucel. SVd demonstrates meaningful activity in patients with penta-refractory MM and prior failure of BCMA/GPRC5D-targeted immunotherapies. The ORR of 61%, disease control in 78% of patients, and median PFS of 4.3 months support further evaluation of SVd in this highly refractory setting after failure of BCMA- and GPRC5D-directed approaches.

ORR was 75.4% (95% CI, 63.1-85.2) and CRR was 35.4% (95% CI, 23.9-48.2). The manufacturing success of ide-cel is reliable and consistently high, and when OOS ide-cel products emerged, they demonstrated consistent clinical efficacy and safety.

P2/3, N=312, Recruiting, Celgene | N=214 --> 312

P2, N=32, Recruiting, Massachusetts General Hospital | Trial primary completion date: Dec 2025 --> Aug 2026

P3, N=79, Active, not recruiting, Celgene | N=618 --> 79 | Trial completion date: Aug 2025 --> Nov 2029