Characterizing EEG and Serum Biomarker Trends in Immune Effector Cell-Associated Neurotoxicity: A Case Series
Andrew Nguyen1, Lila Renteria2, Paul Motika1, H. E. Hinson1
1Oregon Health & Science University, 2Portland State University
Objective:
To characterize electroencephalographic (EEG) trends over time in immune effector cell-associated neurotoxicity syndrome (ICANS) and identify correlations between neuron-derived serum biomarkers of inflammation, neurotoxicity grade, and EEG findings.
Background:
Chimeric antigen receptor T-cell therapy (CAR-T) can be effective for refractory hematologic malignancies, but may be complicated by ICANS. Previous studies link higher peak neurotoxicity grades with EEG background abnormalities and higher incidences of rhythmic and periodic patterns (RPPs).
Design/Methods:
We performed a retrospective analysis of CAR-T patients who were enrolled into an IRB-approved prospective, longitudinal observational study. Data including demographics, ICE scores, and neurologic symptoms were prospectively entered. Serum biomarkers including Ang-1, Ang-2, IL-6, UCH-L1, and S100b were drawn prior to CAR-T and at defined time points thereafter. EEG data was reviewed, with encephalopathy grade defined by American Clinical Neurophysiology Society (ACNS) criteria.
Results:
Forty-five patients were included in the study. Ten patients (22%) developed ICANS. EEG data was available for five (11%) patients, with a median of 35 hours recorded per patient. Zero patients had confirmed electrographic seizures. Median ICE score prior to EEG was 1. Backgrounds were mildly or moderately encephalopathic, with improving organization and faster frequencies over time. GPDs or LPDs of 0.5-2Hz were rare to abundant and gradually improved with time. Focal slowing and sharp waves were common. S100b consistently increased above (average 45%) and Ang-2 decreased below (average 53%) baseline at the time of becoming symptomatic for two patients (drawn within 48 hours before/after EEG was obtained), whereas Ang-1, IL-6, and UCH-L1 had more variable changes.
Conclusions:
Patients with ICANS who underwent EEGs had up to moderate electrographic (and severe clinical) encephalopathy and RPPs that spontaneously improved with time. Higher encephalopathy grade occurred in those with greater S100b increases. Our observations will need to be confirmed in an independent population with serial samples and EEG data on all patients.