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

Corentin Le Cacheux; Audrey Couturier; Clara Sortais; Roch Houot; Morgane Péré; Thomas Gastinne; Amélie Seguin; Jean Reignier; Jean-Baptiste Lascarrou; Jean-Marc Tadié; Quentin Quelven; Emmanuel Canet

doi:10.1186/s13613-024-01247-9

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

Ann Intensive Care. 2024 Jan 31;14(1):20. doi: 10.1186/s13613-024-01247-9.

Authors

Affiliations

¹ Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire Hôtel-Dieu, 30 Bd. Jean Monnet, 44093, Nantes Cedex 1, France. [email protected].
² Clinical Haematology Department, Rennes University Hospital, Rennes University, INSERM U1236, Rennes, France.
³ Haematology Department, Nantes University Hospital, Nantes University, Nantes, France.
⁴ Biostatistics Department, Nantes University Hospital, Nantes University, Nantes, France.
⁵ Service de Médecine Intensive Réanimation, Centre Hospitalier Universitaire Hôtel-Dieu, 30 Bd. Jean Monnet, 44093, Nantes Cedex 1, France.
⁶ ICU, Nantes University, Nantes University Hospital,-Interactions-Performance Research Unit (MIP, UR 4334), Nantes, France.
⁷ ICU, Rennes University Hospital, Rennes University, Rennes, France.

Abstract

Background: Chimeric 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.

Methods: This retrospective observational cohort study included consecutive adults admitted to either of two French ICUs in 2018-2022 within 3 months after CAR-T therapy.

Results: Among 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.

Conclusion: ICU 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.

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