NfL serum levels before and after CAR T-cell transfusion and the interaction of CRS, ICANS, and NfL-post levels. (A) Pretreatment NfL serum levels (NfL-pre) were significantly higher in patients who developed moderate to severe ICANS (ICANS grade 2-4) than in those with no to mild ICANS (ICANS grade 0-1). (B) Multivariable logistic regression adjusting for age, diagnosis (DLBCL vs non-DLBCL), and study center revealed a significant correlation between NfL-pre levels and the severity of ICANS. (C) NfL-post levels were significantly higher than NfL-pre levels for the whole CAR T-cell group in a mixed linear model (fixed factors: CAR T-cell product, diagnosis, age, study center, ICANS severity, and ICANS grade). (D) Posttreatment NfL serum levels (NfL-post) were significantly higher in patients with moderate to severe ICANS (ICANS grade 2-4) than in patients with no to only mild ICANS (ICANS grade 0-1). (E) A significant correlation between NfL-post and ICANS grade was detected in a multivariable logistic regression model after adjustment for age, diagnosis (DLBCL vs non-DLBCL), and study center. (F) Receiver operating characteristics revealed a sensitivity and specificity of NfL-pre to stratify the severity of ICANS after CAR T-cell treatment of 0.88 and 0.50 (area under the curve, 0.711) at a cutoff value of 74.8 pg/mL. (G) Interactions between CRS, ICANS, and NfL-post were analyzed by applying mediation analysis.^11,12  NfL-post levels could account for 28% of the overall effect that CRS had on ICANS. *P < .05; **P < .01; ***P < .001.