Continuous EEG monitoring detects nonconvulsive seizure and Ictal-Interictal Continuum abnormalities in moderate to severe ICANS following systemic CAR-T therapy.

Abstract

Immune Cell Effector Associated Neurotoxicity Syndrome (ICANS) is common amongst patients receiving CD19 targeted Chimeric Antigen Receptor T-cell (CAR-T) therapy. The purpose of this study is to characterize the incidence of seizures and ictal-interictal continuum (IIC) abnormalities in patients with ICANS. Retrospective review of consecutive patients treated with axicabtagene ciloleucel (axi-cel) for recurrent high-grade systemic lymphoma at Stanford Medical Center between 2/2016-6/2019. Electronic medical records (EMR) were reviewed for clinical features, treatment information, EEG data, CRS (cytokine release syndrome)/ICANS severity, and clinical outcomes. Fifty-six patients met inclusion criteria. 85.7% of patients developed CRS, and 58.9% developed ICANS. Twenty-eight patients had EEG monitoring, of whom 26 had ICANS. Median duration of EEG monitoring was 30 hours (range .5-126 hours). Four patients (7.1%) had seizures (1 patient had a clinical generalized seizure, 2 patients had clinical and nonconvulsive seizures, and 1 patient had an isolated non-convulsive seizure). Ictal-interictal continuum abnormalities were common, of which generalized periodic discharges (GPDs) with triphasic morphology and GPDs with epileptiform morphology were most frequently seen. Generalized periodic discharges with triphasic wave morphology were found across Grade 2-3 peak ICANS severity, however the majority (86%) of patients with epileptiform GPDs had Grade 3 peak ICANS severity. Among patients receiving axi-cel, seizure occurred in 7.1% of the total cohort, representing 12% of patients with ICANS. Ictal-interictal continuum abnormalities are also seen in patients with ICANS, most commonly GPDs. 75% of patients with seizures had nonconvulsive seizures supporting the use of continuous video EEG monitoring in this population.