Early serum S100β but not neuron-specific enolase reflects baseline CNS vulnerability in ICANS after CD19 CAR T-cell therapy

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a frequent complication of CD19 CAR T-cell therapy. Although several biomarkers, particularly S100β, have been reported to be associated with ICANS, their biological significance and specificity remain unclear. We retrospectively studied adult patients treated with commercial CD19 CAR T cells between 2020 and 2024, focusing on early serum dynamics of S100β and neuron-specific enolase (NSE). Among 122 treated patients, 72 had complete paired biomarker measurements and were included; 21 (29%) developed ICANS at a median of 6 days after infusion. Prior CNS involvement was significantly more frequent in patients with ICANS (81% vs 35%). ΔS100β was higher in patients with ICANS compared with those without (0.03 vs 0.01 µg/L, p = 0.037), whereas ΔNSE showed no association with ICANS. In multivariable analysis, prior CNS involvement was the only independent factor associated with ICANS (OR 11.2), while ΔS100β did not retain significance. Neither biomarker correlated with ICANS severity or duration. These results indicate that early serum S100β variations mainly reflect baseline CNS vulnerability rather than ICANS-specific neurotoxicity, and that NSE provides no evidence of early neuronal injury detectable in serum.