Score predicts CAR T-cell-associated neurotoxicity

August 2020 Science Eline Feenstra

Chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory hematologic malignant neoplasm causes severe neurologic adverse events ranging from encephalopathy and aphasia to cerebral edema and death. The cause of neurotoxicity is incompletely understood, and its unpredictability is a reason for prolonged hospitalization after CAR T-cell infusion. A study recently published in JAMA neurology focused on clinical and laboratory parameters to predict the risk of neurotoxicity in patients receiving CAR T cell-therapy.

Over a five-year period, 213 patients were followed who underwent CAR T cell therapy with axicabtagene ciloleucel for relapsed or refractory lymphoma. Patients who had previously received CAR T cells or who were treated for mantle cell lymphoma were excluded (n = 9). Patients were followed up for a minimum of 30 days from the date of CAR T-cell infusion. The primary outcomes were measures of performance (accuracy, sensitivity, specificity, area under the curve) of a diagnostic tool to predict the occurrence of CAR-associated neurotoxicity.

Results multivariable score

A total of 204 patients were included in the analysis, of which 126 comprised a derivation cohort (61.8%) and 78 an internal validation cohort (38.2%). In the derivation cohort, 73 patients developed neurotoxicity (57.9%). This number was 45 in the validation cohort (57.7%). Clinical and laboratory values were used to develop a multivariable score that can predict the subsequent development of neurotoxicity. When tested on an internal validation cohort, this score had an area under the curve of 74%, an accuracy of 77%, a sensitivity of 82%, and a specificity of 70%.

In conclusion, the score developed in this study may help predict which patients are likely to experience CAR T-cell–associated neurotoxicity. The score can be used for triaging and resource allocation and may allow a large proportion of patients to be discharged from the hospital early.

Reference

Rubin DB, Jarrah AA, Li K et al. Clinical Predictors of Neurotoxicity After Chimeric Antigen Receptor T-Cell Therapy. JAMA Neurol. 2020 Aug 10;e202703. doi: 10.1001/jamaneurol.2020.2703.

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