# Neuronal injury biomarkers GFAP and neurofilament light chains (NfL) are associated with neurotoxicity and endothelial dysfunction in adult patients treated with antiCD19 CART cells

## TL;DR

This study shows that biomarkers GFAP and NfL can predict neurotoxicity and coagulation issues in patients receiving anti-CD19 CAR-T therapy.

## Contribution

The study identifies GFAP and NfL as predictive biomarkers for ICANS and corticosteroid use in CAR-T-treated patients.

## Key findings

- Baseline GFAP and NfL levels correlate with ICANS development and steroid requirement.
- Elevated NfL and GFAP levels at day 7 correlate with coagulation abnormalities and inflammation.
- These biomarkers suggest pre-existing neuronal susceptibility and endothelial stress in CAR-T patients.

## Abstract

Chimeric antigen receptor T-cell (CAR-T) therapies targeting CD19 have revolutionized the treatment of B-cell malignancies, but their use is frequently complicated by immune effector cell-associated neurotoxicity syndrome (ICANS). The underlying mechanisms include endothelial dysfunction, blood–brain barrier disruption, and neuroinflammation. Circulating biomarkers of neuronal and astroglial injury, such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), may provide insight into ICANS pathophysiology and serve as predictive tools. We conducted a retrospective study of 34 adult patients treated with anti-CD19 CAR-T cells for B-cell malignancies. Serum NfL and GFAP were measured at infusion (day 0) and day 7 using ultrasensitive immunoassays. Baseline GFAP and NfL levels correlated with endothelial activation markers, including mEASIX and lactate dehydrogenase, but not with demographic variables. ICANS of any grade occurred in 34% of patients, and baseline levels of both GFAP and NfL were significantly associated with ICANS development and with steroid requirement. In contrast, changes in biomarker concentrations between day 0 and day 7 were not statistically significant overall, although individual variability was observed. At day 7, elevated NfL levels correlated with laboratory evidence of disseminated intravascular coagulation (DIC), prolonged clotting time, and C-reactive protein elevation. GFAP elevation was also linked to coagulopathy, particularly prolonged clotting time. Baseline serum levels of GFAP and NfL predict the risk of ICANS and the need for corticosteroid intervention in CAR-T-treated adults, supporting their role as biomarkers of pre-existing neuronal susceptibility. Furthermore, their association with coagulation abnormalities underscores the interplay between neurotoxicity, endothelial stress, and systemic inflammation. These findings highlight the potential clinical utility of integrating GFAP and NfL into multimodal biomarker panels to improve risk stratification and management of CAR-T neurotoxicity.