Blood Test Could Predict Neurotoxicity Associated With CAR T-Cell Therapy

By Leah Lawrence - Last Updated: September 20, 2022

The risk of developing immune effector cell-associated neurotoxicity syndrome (ICANS), a complication of CAR T-cell therapy, was associated with a pre-existing neuroaxonal injury that was detectable with a blood test, according to a study published in JAMA Oncology.

Administration of a blood test could help identify which patients are predisposed to developing neurotoxic side effects in the days and weeks after CAR T-cell therapy, according to study researchers.

“Our study suggests that some patients receiving CAR T-cell therapy have previously undetected damage to neurons present at baseline, before we even begin preparing them for this treatment,” said lead author Omar H. Butt, MD, PhD, an instructor in medicine who treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. “We don’t know the origin of this damage, but it appears to predispose them to developing neurotoxic complications. If we understand who is at risk of these complications, we can take early steps to prevent it or reduce the severity.”

The retrospective two-center study looked at plasma neurofilament light chain (NfL) levels in 30 patients with detailed medical and treatment history. A general marker of damage to neurons, the NfL protein has been used to measure or monitor the severity of several neurologic diseases, including Alzheimer’s disease and multiple sclerosis.

NfL levels were measured at 7 time points: baseline, during lymphodepletion, post-infusion day 1, day 3, day, 7, day 14, and day 30.

Patients who developed ICANS had elevations in NfL prior to lymphodepletion and CAR T-cell infusion compared with patients who did not develop ICANS (P<.001). Baseline NfL levels predicted ICANS development with a sensitivity of 0.91 and a specificity of 0.95.

“While unlikely to be the sole driver of ICANS, neural injury reflected by NfL may aid in identifying a high-risk subset of patients undergoing cellular therapy,” the researchers wrote.

There were no associations with ICANS and demographic, oncologic, neurologic or exposure to neurotoxic risk factors, including cytokine release syndrome.

“Measures of NfL in the blood are being used as a way to evaluate the effectiveness of potential new therapies for multiple sclerosis,” said co-senior author Beau M. Ances, MD, PhD, the Daniel J. Brennan Professor of Neurology. “We plan to continue our studies to find the origin of neuronal damage in these cancer patients.”


Assessment of Pretreatment and Posttreatment Evolution of Neurofilament Light Chain Levels in Patients Who Develop Immune Effector Cell–Associated Neurotoxicity Syndrome