EEG before chimeric antigen receptor T-cell therapy and early after onset of immune effector cell-associated neurotoxicity syndrome

Abstract

Background: Immune effector cell-associated neurotoxicity syndrome (ICANS) is common after chimeric antigen receptor T-cell (CAR-T) therapy.

Objective: This study aimed to assess the impact of preinfusion electroencephalography (EEG) abnormalities and EEG findings at ICANS onset for predicting ICANS risk and severity in 56 adult patients with refractory lymphoma undergoing CAR-T therapy.

Study design: EEGs were conducted at the time of lymphodepleting chemotherapy and shortly after onset of ICANS.

Results: Twenty-eight (50%) patients developed ICANS at a median time of 6 days after CAR-T infusion. Abnormal preinfusion EEG was identified as a risk factor for severe ICANS (50% vs. 17%, P = 0.036). Following ICANS onset, EEG abnormalities were detected in 89% of patients [encephalopathy (n = 19, 70%) and/or interictal epileptiform discharges (IEDs) (n = 14, 52%)]. Importantly, IEDs seemed to be associated with rapid progression to higher grades of ICANS within 24 h.

Conclusions: If confirmed in a large cohort of patients, these findings could establish the basis for modifying current management guidelines, enabling the identification of patients at risk of neurotoxicity, and providing support for preemptive corticosteroid use in patients with both initial grade 1 ICANS and IEDs at neurotoxicity onset, who are at risk of neurological impairment.

Keywords: CAR-T (chimeric antigen receptor T-cell); EEG (electroencephalography); ICANS (immune effector cell-associated neurotoxicity syndrome); IEDs (interictal epileptiform discharges).