The clinical picture of ICANS after CAR-T cell therapy in critically ill patients: A retrospective clustering analysis of a multicentre multinational cohort study
Abstract
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.
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BibTeX
@article{vagosmata2026clinical,
title = {{The clinical picture of ICANS after CAR-T cell therapy in critically ill patients: A retrospective clustering analysis of a multicentre multinational cohort study}},
author = {Ana Vagos-Mata and Pedro Castro and Sandrine Valade and Antoine F Carpentier and Alice Gallo de Moraes and Adel Maamar and Muriel Picard and Anne-Sophie Moreau and Sanjay Chawla and Florent Wallet and Kada Klouche and Victoria Metaxa and Nicolas Boissel and Andry van de Louw and Amélie Séguin and Djamel Mokart and Boris Böll and Roberta Di Blasi and Catherine Thieblemont and Nahema Issa and Sara Fernandez and Laveena Munshi and Philippe R. Bauer and Michael Joannidis and Gabriel Moreno-Gonzalez and Lara Zafrani and Michaël Darmon and Élie Azoulay},
journal = {Annals of Intensive Care},
year = {2026},
month = sep,
doi = {10.1016/j.aicoj.2026.100123},
url = {https://hal.science/hal-05742836v2},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - The clinical picture of ICANS after CAR-T cell therapy in critically ill patients: A retrospective clustering analysis of a multicentre multinational cohort study
AU - Ana Vagos-Mata
AU - Pedro Castro
AU - Sandrine Valade
AU - Antoine F Carpentier
AU - Alice Gallo de Moraes
AU - Adel Maamar
AU - Muriel Picard
AU - Anne-Sophie Moreau
AU - Sanjay Chawla
AU - Florent Wallet
AU - Kada Klouche
AU - Victoria Metaxa
AU - Nicolas Boissel
AU - Andry van de Louw
AU - Amélie Séguin
AU - Djamel Mokart
AU - Boris Böll
AU - Roberta Di Blasi
AU - Catherine Thieblemont
AU - Nahema Issa
AU - Sara Fernandez
AU - Laveena Munshi
AU - Philippe R. Bauer
AU - Michael Joannidis
AU - Gabriel Moreno-Gonzalez
AU - Lara Zafrani
AU - Michaël Darmon
AU - Élie Azoulay
PY - 2026
DA - 2026/09/08
JO - Annals of Intensive Care
DO - 10.1016/j.aicoj.2026.100123
UR - https://hal.science/hal-05742836v2
AB - 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.
SN - 2110-5820
ER -