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Multicenter Study
. 2022 Jan 1;50(1):81-92.
doi: 10.1097/CCM.0000000000005149.

Critically Ill Patients Treated for Chimeric Antigen Receptor-Related Toxicity: A Multicenter Study

Cristina Gutierrez  1 , Anne Rain T Brown  2 , Heather P May  3 , Amer Beitinjaneh  4 , R Scott Stephens  5 , Prabalini Rajendram  6 , Joseph L Nates  7 , Stephen M Pastores  8 , Ananda Dharshan  9 , Alice Gallo de Moraes  10 , Matthew K Hensley  11 , Lei Feng  12 , Jennifer N Brudno  13 , Janhavi Athale  14 , Monalisa Ghosh  15 , James N Kochenderfer  16 , Alejandro S Arias  17 , Yi Lin  18 , Colleen McEvoy  19 , Elena Mead  8 , Jason Westin  20 , Natalie Kostelecky  8 , Agrima Mian  21 , Megan M Herr  22
Affiliations
Multicenter Study

Critically Ill Patients Treated for Chimeric Antigen Receptor-Related Toxicity: A Multicenter Study

Cristina Gutierrez et al. Crit Care Med. .

Abstract

Objectives: To report the epidemiology, treatments, and outcomes of adult patients admitted to the ICU after cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome.

Design: Retrospective cohort study.

Setting: Nine centers across the U.S. part of the chimeric antigen receptor-ICU initiative.

Patients: Adult patients treated with chimeric antigen receptor T-cell therapy who required ICU admission between November 2017 and May 2019.

Interventions: Demographics, toxicities, specific interventions, and outcomes were collected.

Results: One-hundred five patients treated with axicabtagene ciloleucel required ICU admission for cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome during the study period. At the time of ICU admission, the majority of patients had grade 3-4 toxicities (66.7%); 15.2% had grade 3-4 cytokine release syndrome and 64% grade 3-4 immune effector cell-associated neurotoxicity syndrome. During ICU stay, cytokine release syndrome was observed in 77.1% patients and immune effector cell-associated neurotoxicity syndrome in 84.8% of patients; 61.9% patients experienced both toxicities. Seventy-nine percent of patients developed greater than or equal to grade 3 toxicities during ICU stay, however, need for vasopressors (18.1%), mechanical ventilation (10.5%), and dialysis (2.9%) was uncommon. Immune Effector Cell-Associated Encephalopathy score less than 3 (69.7%), seizures (20.2%), status epilepticus (5.7%), motor deficits (12.4%), and cerebral edema (7.9%) were more prevalent. ICU mortality was 8.6%, with only three deaths related to cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Median overall survival time was 10.4 months (95% CI, 6.64-not available mo). Toxicity grade or organ support had no impact on overall survival; higher cumulative corticosteroid doses were associated to decreased overall and progression-free survival.

Conclusions: This is the first study to describe a multicenter cohort of patients requiring ICU admission with cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy. Despite severe toxicities, organ support and in-hospital mortality were low in this patient population.

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Conflict of interest statement

This data was accepted to be presented as abstracts and an oral presentation at the Society of Critical Care Medicine Congress in Orlando, FL, 2020. Drs. Gutierrez, Brudno, and Athale received support for article research from the National Institutes of Health. Dr. Gutierrez disclosed the off-label product use of anakinra; she disclosed that she served, and will serve again, in the advisory board for Legend Biotech and Janssen in August 2020. Drs. Gutierrez, May, and McEvoy disclosed the off-label product use of Siltuximab. Dr. Brown received funding from La Jolla Pharmaceutical outside the submitted work. Dr. May disclosed the off-label product use of Corticosteroids. Dr. Beitinjaneh received funding from KITE pharmaceuticals on August 2018. Drs. Brudno and Kochenderfer disclosed government work. Dr. Kochenderfer’s institution received funding from KITE pharmaceuticals, Bristol Meyers Squibb, and Kyverna; he is the principal investigator of Cooperative Research and Development Agreements with Kite, a Gilead Company and Celgene. Dr. Lin as Principal Investigator Mayo Clinic receives compensation for research activities and clinical trials with Kite/Gilead, Janssen, Celgene, BlueBird Bio, Merck, Boston Scientific, Gamida, and Takeda; advisory board with Kite/Gilead, Novartis, Janssen, Legend BioTech, JUNO, Bristol-Myers-Squibb (BMS), Celgene, BlueBird Bio, and Ethos; Data and Safety Monitoring Board: Sorrento; and steering committee: Celgene, Janssen, and Legend BioTech. Dr. McEvoy received funding from United Therapeutics. Dr. Westin received funding from BMS, Novartis, Kite Gilead, Juno Celgene, Genentech, AstraZeneca, Morphosys, and ADC Therapeutics. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Figures

Figure 1.
Figure 1.
Inclusion criteria for CAR T-cell patients treated for the period of November 2017-May 2019 in all institutions.
Figure 2.
Figure 2.
Overall survival of patients admitted to the ICU with CRS and ICANS after CAR T-cell therapy.
Figure 3.
Figure 3.
Overall survival, progression free survival and cumulative corticosteroid dose.
See this image and copyright information in PMC

Comment in

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