GFAP and NfL increase during neurotoxicity from high baseline levels in pediatric CD19-CAR T-cell patients.

There is a need for biomarkers to predict and measure the severity of immune effector cell associated neurotoxicity syndrome (ICANS). Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are well validated biomarkers of astroglial and neuronal injury, respectively. We hypothesized that pretreatment GFAP and NfL levels can predict the risk of subsequent ICANS, and that increases of GFAP and NfL levels during treatment reflect ICANS severity. We measured CSF GFAP (cGFAP) and NfL (cNfL) as well as serum NfL (sNfL) levels in pretreatment and day 7-10 post CAR T samples in 3 pediatric cohorts treated with CD19- or CD19/CD22-directed CAR T cells. cGFAP and cNfL increased during grade≥1 ICANS in patients treated with CD19-directed CAR T cells but not in those who received CD19/CD22-directed CAR T cells. sNfL levels did not increase during ICANS. Pre-lymphodepletion cGFAP, cNfL, and sNfL levels were not predictive of subsequent ICANS. Elevated baseline levels of cGFAP were associated with history of transplant, patients with prior CNS radiation had higher cNfL levels, and elevated baseline levels of sNfLwere associated with a history of peripheral neuropathy. cGFAP and cNfL may be useful biomarkers to measure the severity of CNS injury during ICANS in children. Elevated baseline levels of cGFAP, cNfL and sNfL likely reflect the cumulative injury to the central and peripheral nervous system from prior treatment. However, levels of any of the three biomarkers prior to CAR T cell infusion did not predict ICANS risk.