Advancing CAR-T Cell Therapy: Biomarker Discovery and Toxicity Management in Pediatric and Young-Adult Populations

CAR-T cell therapy has substantially improved treatment options for relapsed or refractory hematologic malignancies, but clinically important toxicities remain, particularly cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and treatment-related cytopenias. This article provides a structured evidence review focused on biomarker discovery, toxicity assessment, and management in pediatric and young-adult populations. Published evidence includes pediatric and young-adult clinical studies, broader CAR-T toxicity syntheses, and biomarker studies involving glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL). A pediatric real-world cohort reported complete remission in 79% of patients at one month on an intent-to-treat basis, while a broader, mixed pediatric-and-adult meta-analysis reported an all-grade CRS rate of 77%; these estimates come from different evidence bases and should not be interpreted as a single pooled estimate. The same pediatric real-world study reported neurotoxicity in 18.1% of evaluable patients, while a separate systematic review and meta-analysis drawing on a mixed and adult-predominant evidence base reported thrombocytopenia in 45.8% of CAR-T recipients. Current evidence supports GFAP and NfL as promising markers of neurological injury, although their predictive performance and clinical thresholds in children remain incompletely established. The review therefore proposes a conceptual biomarker-guided framework that links baseline risk assessment, serial monitoring, clinical grading, intervention, and reassessment. The evidence also highlights antigen loss, T-cell dysfunction, and the need for better pediatric-specific validation of toxicity biomarkers. Future work should prioritize prospective pediatric cohorts, harmonized biomarker definitions, and transparent, population-specific reporting of treatment outcomes.