TY - JOUR
T1 - Outcomes in patients treated with chimeric antigen receptor T-cell therapy who were admitted to intensive care (CARTTAS)
T2 - an international, multicentre, observational cohort study
AU - Nine-I investigators
AU - Azoulay, Élie
AU - Castro, Pedro
AU - Maamar, Adel
AU - Metaxa, Victoria
AU - de Moraes, Alice Gallo
AU - Voigt, Louis
AU - Wallet, Florent
AU - Klouche, Kada
AU - Picard, Muriel
AU - Moreau, Anne Sophie
AU - Van De Louw, Andry
AU - Seguin, Amélie
AU - Mokart, Djamel
AU - Chawla, Sanjay
AU - Leroy, Julien
AU - Böll, Boris
AU - Issa, Nahema
AU - Levy, Bruno
AU - Hemelaar, Pleun
AU - Fernandez, Sara
AU - Munshi, Laveena
AU - Bauer, Philippe
AU - Schellongowski, Peter
AU - Joannidis, Michael
AU - Moreno-Gonzalez, Gabriel
AU - Galstian, Gennadii
AU - Darmon, Michael
AU - Valade, Sandrine
AU - Zafrani, Lara
AU - Mariotte, Eric
AU - Lemiale, Virginie
AU - Arnulf, Bertrand
AU - Boissel, Nicolas
AU - Thieblemont, Catherine
AU - Rabian, Florence
AU - Harel, Stéphanie
AU - Di Blasi, Roberta
AU - Delgado, Julio
AU - Ortiz, Valentin
AU - Blaise, Didier
AU - Fürst, Sabine
AU - Legrand, Faezeh
AU - Chabannon, Christian
AU - Forcade, Edouard
AU - Gros, François Xavier
AU - Borel, Cécile
AU - Huynh, Anne
AU - Récher, Christian
AU - Rudzki, Jakob
AU - Rakszawski, Kevin
N1 - Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/5
Y1 - 2021/5
N2 - Background: Chimeric antigen receptor (CAR) T-cell therapy can induce side-effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS), which often require intensive care unit admission. The aim of this study was to describe management of critically ill CAR T-cell recipients in intensive care. Methods: This international, multicentre, observational cohort study was done in 21 intensive care units in France, Spain, the USA, the UK, Russia, Canada, Germany, and Austria. Eligible patients were aged 18 years or older; had received CAR T-cell therapy in the past 30 days; and had been admitted to intensive care for any reason. Investigators retrospectively included patients admitted between Feb 1, 2018, and Feb 1, 2019, and prospectively included patients admitted between March 1, 2019, and Feb 1, 2020. Demographic, clinical, laboratory, treatment, and outcome data were extracted from medical records. The primary endpoint was 90-day mortality. Factors associated with mortality were identified using a Cox proportional hazard model. Findings: 942 patients received CAR T-cell therapy, of whom 258 (27%) required admission to intensive care and 241 (26%) were included in the analysis. Admission to intensive care was needed within median 4·5 days (IQR 2·0–7·0) of CAR T-cell infusion. 90-day mortality was 22·4% (95% CI 17·1–27·7; 54 deaths). At initial evaluation on admission, isolated cytokine release syndrome was identified in 101 patients (42%), cytokine release syndrome and ICANS in 93 (39%), and isolated ICANS in seven (3%) patients. Grade 3–4 cytokine release syndrome within 1 day of admission to intensive care was found in 50 (25%) of 200 patients and grade 3–4 ICANS in 38 (35%) of 108 patients. Bacterial infection developed in 30 (12%) patients. Life-saving treatments were used in 75 (31%) patients within 24 h of admission to intensive care, primarily vasoactive drugs in 65 (27%) patients. Factors independently associated with 90-day mortality by multivariable analysis were frailty (hazard ratio 2·51 [95% CI 1·37–4·57]), bacterial infection (2·12 [1·11–4·08]), and lifesaving therapy within 24 h of admission (1·80 [1·05–3·10]). Interpretation: Critical care management is an integral part of CAR T-cell therapy and should be standardised. Studies to improve infection prevention and treatment in these high-risk patients are warranted. Funding: Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique.
AB - Background: Chimeric antigen receptor (CAR) T-cell therapy can induce side-effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS), which often require intensive care unit admission. The aim of this study was to describe management of critically ill CAR T-cell recipients in intensive care. Methods: This international, multicentre, observational cohort study was done in 21 intensive care units in France, Spain, the USA, the UK, Russia, Canada, Germany, and Austria. Eligible patients were aged 18 years or older; had received CAR T-cell therapy in the past 30 days; and had been admitted to intensive care for any reason. Investigators retrospectively included patients admitted between Feb 1, 2018, and Feb 1, 2019, and prospectively included patients admitted between March 1, 2019, and Feb 1, 2020. Demographic, clinical, laboratory, treatment, and outcome data were extracted from medical records. The primary endpoint was 90-day mortality. Factors associated with mortality were identified using a Cox proportional hazard model. Findings: 942 patients received CAR T-cell therapy, of whom 258 (27%) required admission to intensive care and 241 (26%) were included in the analysis. Admission to intensive care was needed within median 4·5 days (IQR 2·0–7·0) of CAR T-cell infusion. 90-day mortality was 22·4% (95% CI 17·1–27·7; 54 deaths). At initial evaluation on admission, isolated cytokine release syndrome was identified in 101 patients (42%), cytokine release syndrome and ICANS in 93 (39%), and isolated ICANS in seven (3%) patients. Grade 3–4 cytokine release syndrome within 1 day of admission to intensive care was found in 50 (25%) of 200 patients and grade 3–4 ICANS in 38 (35%) of 108 patients. Bacterial infection developed in 30 (12%) patients. Life-saving treatments were used in 75 (31%) patients within 24 h of admission to intensive care, primarily vasoactive drugs in 65 (27%) patients. Factors independently associated with 90-day mortality by multivariable analysis were frailty (hazard ratio 2·51 [95% CI 1·37–4·57]), bacterial infection (2·12 [1·11–4·08]), and lifesaving therapy within 24 h of admission (1·80 [1·05–3·10]). Interpretation: Critical care management is an integral part of CAR T-cell therapy and should be standardised. Studies to improve infection prevention and treatment in these high-risk patients are warranted. Funding: Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique.
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U2 - 10.1016/S2352-3026(21)00060-0
DO - 10.1016/S2352-3026(21)00060-0
M3 - Article
C2 - 33894170
AN - SCOPUS:85104396949
SN - 2352-3026
VL - 8
SP - e355-e364
JO - The Lancet Haematology
JF - The Lancet Haematology
IS - 5
ER -