Early Recognition of ICANS with a Novel EEG-based DeltaWave Detection System in Patients Receiving CAR T-cell Therapy Open Access

• Polymorphic Delta Activity (PDA) scores can recognize the occurrence of ICANS any grade early, with an AUC of 82.7%.

• PDA scores (≥ 4) can recognize the onset of ICANS a median of 68 hours prior to clinical symptoms.

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a potential life-threatening treatment-related adverse event of chimeric antigen receptor (CAR) T-cell therapy. Early recognition of patients at risk of ICANS is crucial and may guide use of steroids in these patients. Measuring polymorphic delta activity (PDA) may offer an early and reliable recognition for the onset of ICANS. Therefore, a prospective study was performed on adult patients with Large B-cell lymphoma (LBCL) or B-cell Acute Lymphoblastic Leukemia (B-ALL) treated with CAR T-cell therapy. Before and twice daily after CAR T-cell infusion, patients underwent a single channel electroencephalogram (EEG) recording (Fp2-Pz), from which a PDA score (1-5) was automatically generated. Concurrently, ICANS grade was assessed by the treating physician based on the patient’s status and the immune effector cell encephalopathy (ICE) score. Twenty-six patients were subjected to analysis, of whom nine (35%) had a tumor localization within the central nervous system. PDA scores ≥ 4 showed an excellent discrimination between ICANS (n=14) and no ICANS (n=12) with an AUC of 82.7%, an accuracy of 84.6%, sensitivity of 78.6%, specificity of 91.7%, PPV of 91.7%, and NPV of 78.6%. Of high interest, a PDA score ≥ 4 preceded the clinical manifestation of ICANS with a median lead time of 68.0 hours (IQR: 8.0-107.0). PDA scores provide an accurate method to recognize ICANS prior to clinical symptoms, in patients receiving CAR T-cell therapy. This makes it an attractive tool for implementation in daily clinical care and enables early intervention strategies of patients developing ICANS.