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Title: Outcomes in patients treated with chimeric antigen receptor T-cell therapy who were admitted to intensive care (CARTTAS): an international, multicentre, observational cohort study
Author: Azoulay, Élie
Castro, Pedro
Maamar, Adel
Gallo de Moraes, Alice
Voigt, Louis
Wallet, Florent
Klouche, Kada
Picard, Muriel
Moreau, Anne Sophie
Van de Louw, Andry
Seguin, Amélie
Mokart, Djamel
Chawla, Sanjay
Leroy, Julien
Böll, Boris
Issa, Nahema
Levy, Bruno
Hemelaar, Pleun
Fernandez, Sara
Munshi, Laveena
Bauer, Philippe
Schellongowski, Peter
Joannidis, Michael
Moreno Gonzalez, Gabriel
Galstian, Gennadii
Darmon, Michael
Valade, Sandrine
Zafrani, Lara
Mariotte, Eric
Lemiale, Virginie
Arnulf, Bertrand
Boissel, Nicolas
Thieblemont, Catherine
Rabian, Florence
Harel, Stéphanie
Di Blasi, Roberta
Delgado, Julio
Ortiz, Valentin
Blaise, Didier
Fürst, Sabine
Legrand, Faezeh
Chabannon, Christian
Forcade, Edouard
Gros, François Xavier
Borel, Cécile
Huynh, Anne
Récher, Christian
Rudzki, Jakob
Rakszawski, Kevin
Sesques, Pierre
Bachy, Emmanuel
Salles, Gilles
Perales, Miguel A.
Wohlfarth, Philipp
Staudingert, Thomas
Jäger, Ulrich
Cartron, Guillaume
Fégueux, Nathalie
Ceballos, Patrice
Platon, Laura
Gastinne, Thomas
Tessoulin, Benoit
Le Bourgeois, Amandine
Gavrilina, Olga
Sureda, Anna
Mussetti, Alberto
Garcia Borrega, Jorge
Borchmann, Peter
Lin, Yi
Benjamin, Reuben
Guibert, Sophie de
Quelven, Quentin
Yakoub Agha, Ibrahim
Beauvais, David
Rubio, Marie Therese
Metaxa, Victoria
Keywords: Assaigs clínics
Cura dels malalts
Medicina intensiva
Clinical trials
Care of the sick
Critical care medicine
Issue Date: 1-May-2021
Publisher: Elsevier BV
Abstract: 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.
Note: Versió postprint del document publicat a:
It is part of: The Lancet Haematology, 2021, vol. 8, num. 5, p. e355-e364
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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