Features and outcomes of patients admitted to the ICU for chimeric antigen receptor T cell-related toxicity: a French multicentre cohort

Corentin Le Cacheux (1) , Audrey Couturier (2) , Clara Sortais (1) , Roch Houot (2) , Morgane Pere (1) , Thomas Gastinne (1) , Amélie Séguin (1) , Jean Reignier (1) , Jean-Baptiste Lascarrou (1) , Jean-Marc Tadie (3) , Quentin Quelven (3) , Emmanuel Canet (1)

1 CHU Nantes - Centre Hospitalier Universitaire de Nantes
2 MOBIDIC - Microenvironment and B-cells: Immunopathology,Cell Differentiation, and Cancer
3 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]

BackgroundChimeric antigen receptor T-cell (CAR-T) therapy is increasingly used in patients with refractory haematological malignancies but can induce severe adverse events. We aimed to describe the clinical features and outcomes of patients admitted to the intensive care unit (ICU) after CAR-T therapy.MethodsThis retrospective observational cohort study included consecutive adults admitted to either of two French ICUs in 2018-2022 within 3 months after CAR-T therapy.ResultsAmong 238 patients given CAR-T therapy, 84 (35.3%) required ICU admission and were included in the study, a median of 5 [0-7] days after CAR-T infusion. Median SOFA and SAPSII scores were 3 [2-6] and 39 [30-48], respectively. Criteria for cytokine release syndrome were met in 80/84 (95.2%) patients, including 18/80 (22.5%) with grade 3-4 toxicity. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 46/84 (54.8%) patients, including 29/46 (63%) with grade 3-4 toxicity. Haemophagocytic lymphohistiocytosis was diagnosed in 15/84 (17.9%) patients. Tocilizumab was used in 73/84 (86.9%) patients, with a median of 2 [1-4] doses. Steroids were given to 55/84 (65.5%) patients, including 21/55 (38.2%) given high-dose pulse therapy. Overall, 23/84 (27.4%) patients had bacterial infections, 3/84 (3.6%) had fungal infections (1 invasive pulmonary aspergillosis and 2 Mucorales), and 2 (2.4%) had cytomegalovirus infection. Vasopressors were required in 23/84 (27.4%), invasive mechanical ventilation in 12/84 (14.3%), and dialysis in 4/84 (4.8%) patients. Four patients died in the ICU (including 2 after ICU readmission, i.e., overall mortality was 4.8% of patients). One year after CAR-T therapy, 41/84 (48.9%) patients were alive and in complete remission, 14/84 (16.7%) were alive and in relapse, and 29/84 (34.5%) had died. These outcomes were similar to those of patients never admitted to the ICU.ConclusionICU admission is common after CAR-T therapy and is usually performed to manage specific toxicities. Our experience is encouraging, with low ICU mortality despite a high rate of grade 3-4 toxicities, and half of patients being alive and in complete remission at one year.

Mots clés: Chimeric antigen receptor T Cell; Intensive care unit; Cytokine release syndrome; Immune effector cell-associated neurotoxicity syndrome; Haemophagocytic lymphohistiocytosis; Sepsis; Mortality

Domaines: Sciences du Vivant [q-bio]

Corentin Le Cacheux, Audrey Couturier, Clara Sortais, Roch Houot, Morgane Pere, et al.. Features and outcomes of patients admitted to the ICU for chimeric antigen receptor T cell-related toxicity: a French multicentre cohort. Annals of Intensive Care, 2024, Annals of Intensive Care, 14 (1), ⟨10.1186/s13613-024-01247-9⟩. ⟨hal-04443563⟩