Automated detection of immune effector cell‐associated neurotoxicity syndrome via quantitative EEG

Author:

Eckhardt Christine A.1234ORCID,Sun Haoqi123,Malik Preeti123,Quadri Syed123,Santana Firme Marcos123,Jones Daniel K.1235,van Sleuwen Meike123,Jain Aayushee13,Fan Ziwei123,Jing Jin123,Ge Wendong123,Danish Husain H.124,Jacobson Caron A.6,Rubin Daniel B.12,Kimchi Eyal Y.12,Cash Sydney S.12,Frigault Matthew J.278,Lee Jong Woo24ORCID,Dietrich Jorg129,Westover M. Brandon1239

Affiliation:

1. Department of Neurology Massachusetts General Hospital Boston Massachusetts 02114 USA

2. Harvard Medical School Boston Massachusetts 02115 USA

3. Clinical Data Animation Center Massachusetts General Hospital Boston Massachusetts 02114 USA

4. Department of Neurology Brigham and Women's Hospital Boston Massachusetts 02115 USA

5. Brigham Young University Provo Utah 84602 USA

6. Dana Farber Cancer Institute Boston Massachusetts 02115 USA

7. Cellular Immunotherapy Program Massachusetts General Hospital Cancer Center Boston Massachusetts 02114 USA

8. Blood and Marrow Transplant Program Massachusetts General Hospital Boston Massachusetts 02114 USA

9. Massachusetts General Hospital Cancer Center for Brain Health Boston Massachusetts 02114 USA

Abstract

AbstractObjectiveTo develop an automated, physiologic metric of immune effector cell‐associated neurotoxicity syndrome among patients undergoing chimeric antigen receptor‐T cell therapy.MethodsWe conducted a retrospective observational cohort study from 2016 to 2020 at two tertiary care centers among patients receiving chimeric antigen receptor‐T cell therapy with a CD19 or B‐cell maturation antigen ligand. We determined the daily neurotoxicity grade for each patient during EEG monitoring via chart review and extracted clinical variables and outcomes from the electronic health records. Using quantitative EEG features, we developed a machine learning model to detect the presence and severity of neurotoxicity, known as the EEG immune effector cell‐associated neurotoxicity syndrome score.ResultsThe EEG immune effector cell‐associated neurotoxicity syndrome score significantly correlated with the grade of neurotoxicity with a median Spearman's R2 of 0.69 (95% CI of 0.59–0.77). The mean area under receiving operator curve was greater than 0.85 for each binary discrimination level. The score also showed significant correlations with maximum ferritin (R2 0.24, p = 0.008), minimum platelets (R2 –0.29, p = 0.001), and dexamethasone usage (R2 0.42, p < 0.0001). The score significantly correlated with duration of neurotoxicity (R2 0.31, p < 0.0001).InterpretationThe EEG immune effector cell‐associated neurotoxicity syndrome score possesses high criterion, construct, and predictive validity, which substantiates its use as a physiologic method to detect the presence and severity of neurotoxicity among patients undergoing chimeric antigen receptor T‐cell therapy.

Funder

American Academy of Sleep Medicine Foundation

American Federation for Aging Research

Glenn Foundation for Medical Research

National Institute of Mental Health

National Institute of Neurological Disorders and Stroke

National Science Foundation

NIH Clinical Center

Publisher

Wiley

Subject

Neurology (clinical),General Neuroscience

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