Association of Neurofilament Light Chain Levels With ICANS Risk After CAR T-Cell Therapy

Get Permission

In a retrospective study reported in JAMA Oncology, Butt et al found significantly higher pretreatment neurofilament light chain levels in patients who did vs did not develop immune effector cell–associated neurotoxicity syndrome (ICANS) after CD19 chimeric antigen receptor (CAR) T-cell therapy.

The study included 30 patients who received CAR T-cell therapy at Washington University or Case Western Reserve University. Among these, 11 developed ICANS, which was grade 1 or 2 in 4 and grade ≥ 3 in 7. Neurofilament light chain levels were measured at baseline (prelymphodepletion); during lymphodepletion; and on days 1, 3, 7, 14, and 30 after CAR T-cell infusion.

Key Findings

Mean neurofilament light chain levels at baseline were 29.4 pg/mL among patients without ICANS vs 87.6 pg/mL among those with ICANS (P < .001). Mean levels were 115.3 pg/mL among those with grade 1 or 2 ICANS and 71.7 pg/mL among those with grade ≥ 3 ICANS (no significant difference).

Baseline neurofilament light chain level was a highly accurate predictor of ICANS, with a receiver operating characteristic area under the curve value of 0.96, a sensitivity of 91%, and a specificity of 95%. In addition, baseline neurofilament light chain level correlated with ICANS grade (r = 0.74, P < .001), and neurofilament light chain levels remained elevated in patients who developed ICANS at all time points through 30 days postinfusion, with a correlation with ICANS severity observed at all time points.

On multivariate analysis, no significant associations were observed between baseline neurofilament light chain levels and potential risk factors, including demographic (age, sex), oncologic (tumor burden, history of central nervous system [CNS] involvement), and neurologic factors (history of nononcologic CNS disease or neuropathy), or exposure to neurotoxic treatment (vincristine, cytarabine, methotrexate, or CNS radiotherapy).

The investigators concluded, “In a subset of patients in this cross-sectional study, the risk of developing ICANS was associated with preexisting neuroaxonal injury that was quantifiable with plasma [neurofilament light chain] level. This latent neuroaxonal injury was present prior to drug administration but was not associated with historic neurotoxic therapies or nononcologic neurologic disease. Preinfusion [neurofilament light chain level] may further permit early screening and identification of patients most at risk for ICANS. Additional studies are needed to determine utility [of neurofilament light chain level] as a predictive biomarker for early (preemptive or prophylactic) intervention and to delineate the origin of this underlying neural injury.”

Omar H. Butt, MD, PhD, of Siteman Cancer Center, Washington University, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was supported by the McDonnell Center for Systems Neuroscience at Washington University, National Cancer Institute, National Institute of Neurological Disorders and Stroke, and others. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.