Factors Associated with Immune Effector Cell-Associated Neurotoxicity Syndrome in Adults with Hematological Malignancies Undergoing Chimeric Antigen Receptor T-Cell Therapy: A Systematic Review

Objectives: We systematically appraised studies investigating factors associated with ICANS development after CAR-T cell therapies in adults with hematological malignancies and estimated ICANS prevalence. Method: We conducted a systematic review (SR) in 4 databases following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies published from 2010 to December 2024. We estimated ICANS prevalence with exact binomial and score test-based 95% confidence intervals. We applied the Freeman-Tukey double arcsine transformation to stabilize variances within random-effects models using the Metaprop command in Stata. Results: Sixteen studies (14 retrospective, n = 135, and 2 prospective, n = 300) were included in this SR. The sample comprised adults with various hematological malignancies who received anti-CD19 anti-BCMA. Some clinical factors seem to be associated with ICANS incidence and severity. In retrospective studies, the pooled prevalence was 41% (95% CI: 31%-51%) for all grades of ICANS and 20% (95% CI: 13%-28%) for grade 3 ICANS. In prospective studies, the pooled prevalence was 51% (95% CI: 45%-56%). Conclusions: Approximately half of hematological patients undergoing CAR T therapy develop ICANS. Although some factors may contribute to the development of ICANS, limited studies and samples, the retrospective nature of the majority of studies, and the discordance among the results preclude certain risk factors conclusions. Implications for Nursing Practice: Nurses play a pivotal role in post-treatment monitoring in the early detec- tion and management of ICANS, given their direct and continuous patient interaction. Increasing nurses’ awareness of potential risk factors for ICANS can enhance their vigilance and effectiveness in managing this condition.