(C-223) Chimeric Antigen Receptor Therapy (CAR T) Therapy and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): A Systematic Review and Meta-analysis

Background: CAR T-cell therapy, a specialized subset of adoptive immunotherapy, represents an advanced form of cell-based gene therapy. This modality has shown promise in treating hematologic malignancies, such as non-Hodgkin lymphoma (NHL). Subtypes of NHL include diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and multiple myeloma .Notably, CAR T-cell therapy has challenges, such as ICANS. The incidence and severity of ICANS vary across different CAR T-cell therapies and patient populations, emphasizing the need to clarify its severity and impact

Objectives: We conducted a meta analysis to evaluate the incidence and severity of ICANS in patients treated with various types of CAR T therapy treatments in a broader population of hematological malignancies.

Methods: Electronic databases such as PubMed, Embase, and Cochrane Library were searched from inception until February 16, 2024, to identify relevant articles using search terms related to CAR T therapies and neurotoxicity. A total of 259 articles underwent full-text review. A random effects model (Der Simonian and Laird method) was employed to pool the incidence and generate the 95% Cl. Subgroup analyses by ICANS severity grades, lymphoma subtypes (diffuse large B-cell lymphoma, primary mediastinal lymphoma, and transformed follicular lymphoma vs. diffuse large B-cell lymphoma, high-grade B-cell lymphoma and transformed follicular lymphoma), and age (≤ 60 vs. > 60 years) were presented.

Results: In patients with LBCL, the pooled incidence of ICANS was lower for tisagenlecleucel (14.4%, 95% CI: 11.1-18.6, I² = 66.2%) than for axicabtagene ciloleucel (46.6%, 95% CI: 41.1-52.1, I² = 67%). The direction of these results did not materially change when stratifying by ICANS severity, lymphoma subtype, and age. In patients with MM, the pooled incidence of ICANS was lower for idecabtagene vicleucel (18.3%, 95% CI: 15.4-21.5, I² = 0%) than for ciltacabtagene autoleucel (10.4%, 95% CI: 5.2-19.9, I² = 68.3%). In patients with MCL, the pooled incidence of ICANS was relatively high (61.2%, 95% CI: 54.2–67.8, I² = 0.2%) for brexucabtagene autoleucel. Moreover, the pooled incidence of severe ICANS was lower than that of less severe ICANS for each of tisa-cel, axi-cel, ide-cel, and cilta-cel but not for brexu-cel.

Conclusions: For patients with LBCL, tisa-cel demonstrated a better safety profile compared to axi-cel across all grades of ICANS, lymphoma subtypes, and age categories. For patients with MM, cilta-cel appeared safer than ide-cel across all grades of ICANS. Brexu-cel appeared to have a relatively high incidence of ICANS in patients with MCL. Future comparative studies are needed to compare treatments while adjusting for confounders such as bridging therapies and pre-steroid interventions