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

Christine A Eckhardt, Haoqi Sun, Preeti Malik, Syed Quadri, Marcos Santana Firme, Daniel K Jones, Meike van Sleuwen, Aayushee Jain, Ziwei Fan, Jin Jing, Wendong Ge, Husain H Danish, Caron A Jacobson, Daniel B Rubin, Eyal Y Kimchi, Sydney S Cash, Matthew J Frigault, Jong Woo Lee, Jorg Dietrich, M Brandon Westover

Journal: Annals of clinical and translational neurology 2023;10(10):1776-1789

PMID: 37545104

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Abstract

OBJECTIVE

To develop an automated, physiologic metric of immune effector cell-associated neurotoxicity syndrome among patients undergoing chimeric antigen receptor-T cell therapy.

METHODS

We 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.

RESULTS

The EEG immune effector cell-associated neurotoxicity syndrome score significantly correlated with the grade of neurotoxicity with a median Spearman's R 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 (R 0.24, p = 0.008), minimum platelets (R -0.29, p = 0.001), and dexamethasone usage (R 0.42, p < 0.0001). The score significantly correlated with duration of neurotoxicity (R 0.31, p < 0.0001).

INTERPRETATION

The 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.

Address: Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.; Harvard Medical School, Boston, Massachusetts, 02115, USA.; Clinical Data Animation Center, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.; Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.; Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.; Harvard Medical School, Boston, Massachusetts, 02115, USA.; Clinical Data Animation Center, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.; Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.; Harvard Medical School, Boston, Massachusetts, 02115, USA.; Clinical Data Animation Center, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.; Brigham Young University, Provo, Utah, 84602, USA.; Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.; Clinical Data Animation Center, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.; Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.; Harvard Medical School, Boston, Massachusetts, 02115, USA.; Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.; Dana Farber Cancer Institute, Boston, Massachusetts, 02115, USA.; Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.; Harvard Medical School, Boston, Massachusetts, 02115, USA.; Harvard Medical School, Boston, Massachusetts, 02115, USA.; Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, 02114, USA.; Blood and Marrow Transplant Program, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.; Harvard Medical School, Boston, Massachusetts, 02115, USA.; Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, 02115, USA.; Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.; Harvard Medical School, Boston, Massachusetts, 02115, USA.; Massachusetts General Hospital Cancer Center for Brain Health, Boston, Massachusetts, 02114, USA.; Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.; Harvard Medical School, Boston, Massachusetts, 02115, USA.; Clinical Data Animation Center, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.; Massachusetts General Hospital Cancer Center for Brain Health, Boston, Massachusetts, 02114, USA.

DOI: 10.1002/acn3.51866

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MeSH Terms: Humans, Receptors, Chimeric Antigen, Retrospective Studies, Adaptor Proteins, Signal Transducing, Electroencephalography