The Clinical Picture of ICANS after CAR-T Cell Therapy in Critically Ill Patients: A Retrospective Clustering Analysis of a Multicentre Multinational Cohort Study

CAR T-cell therapy carries significant risks, including ICANS. There is limited data on ICANS presentation and outcomes in patients admitted to ICU and it is still challenging to predict those who will have severe ICANS. This is a pre-planned substudy of an international, multicenter, observational cohort study of 241 CAR T-cell recipients for hematological malignancies, admitted to the ICU, focusing on those who developed ICANS. We aimed for a detailed description of symptoms and hierarchical clustering analysis was used to identify distinct patterns of neurological symptom presentation. ICANS was identified in 100 patients (41.5%), median age of 61 years. Most patients (93%) had non-Hodgkin lymphoma. Severe ICANS occurred in 38% of patients, associated with longer duration of symptoms (p = 0.02). On the whole cohort, the median duration of neurological symptoms was 5 (IQR 1-8) days and was also longer for patients with isolated ICANS (median of 16 days (IQR 11-24, p = 0.001)). Hierarchical clustering revealed four distinct clusters with minimal symptom overlap: Cluster 1: Mild or no symptoms, primarily confusion (11.2%); Cluster 2: High incidence of confusion (78.9%) and drowsiness (47.4%), with significant risks of seizures (42.1%) and coma (21.1%); Cluster 3: Predominantly tremor (75%) and attention deficit (37.5%); Cluster 4: High incidence of aphasia (70.3%), dysgraphia (37.8%), and disorientation (27%). The clustering of neurological symptoms was statistically significant (p < 0.001). This study provides a detailed characterization of ICANS, highlighting distinct patterns of neurological symptoms. These findings could inform clinicians, particularly regarding the risk and timing of ICU admission.