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Alice Zhou, MD, PhD, and Omar Butt, MD, PhD, on Investigating Associations With CAR T Toxicities

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The medical oncologists at Washington University School of Medicine in St. Louis discussed background to their research on associations between neurofilament light and neurotoxicity.

“We still don't have that good of an idea of what's going on, especially with neurotoxicity... It's very important to sort of know that mechanism, where it's coming from, but also to identify the people who will develop neurotoxicity because at this point, we don't really know who's going to develop the severe side effects that can be fatal. It'd be nice to advise people who are getting this potentially lifesaving therapy,what is their likelihood of having issues or complications down the line.”

Patients treated with chimeric antigen receptor (CAR) T-cell therapy’s risk of developing immune effector cell–associated neurotoxicity syndrome (ICANS) is associated with plasma neurofilament light chain (NfL) levels, according to a paper published in JAMA Oncology.

First author Omar H. Butt, MD, PhD, and second author Alice Y. Zhou, MD, PhD, both medical oncologists at Washington University School of Medicine in St. Louis, evaluated data from 30 patients treated with CAR T-cell therapy for diffuse large B-cell lymphoma in a retrospective, 2-center study and found that patients who developed any grade ICANS had NfL elevations (mean, 87.6 pg/mL) prior to lymphodepletion and CAR T-cell infusion compared with those who did not develop ICANS (mean, 29.4 pg/mL; P < .001).

CGTLive spoke with Butt and Zhou to learn more about the unmet needs and issues that remain with toxicities in cell therapies with both ICANS and cytokine release syndrome among other toxicities. They discussed how studying the central nervous system of patients that developed toxicities led them to conduct the research.

REFERENCE
Butt OH, Zhou AY, Caimi PF, et al. Assessment of pretreatment and posttreatment evolution of neurofilament light chain levels in patients who develop immune effector cell–associated neurotoxicity syndrome. JAMA Oncol. Published online September 01, 2022. doi:10.1001/jamaoncol.2022.3738