TY - JOUR
T1 - Critically Ill Patients Treated for Chimeric Antigen Receptor-Related Toxicity
T2 - A Multicenter Study
AU - Gutierrez, Cristina
AU - Brown, Anne Rain T.
AU - May, Heather P.
AU - Beitinjaneh, Amer
AU - Stephens, R. Scott
AU - Rajendram, Prabalini
AU - Nates, Joseph L.
AU - Pastores, Stephen M.
AU - Dharshan, Ananda
AU - De Moraes, Alice Gallo
AU - Hensley, Matthew K.
AU - Feng, Lei
AU - Brudno, Jennifer N.
AU - Athale, Janhavi
AU - Ghosh, Monalisa
AU - Kochenderfer, James N.
AU - Arias, Alejandro S.
AU - Lin, Yi
AU - McEvoy, Colleen
AU - Mead, Elena
AU - Westin, Jason
AU - Kostelecky, Natalie
AU - Mian, Agrima
AU - Herr, Megan M.
N1 - Publisher Copyright:
Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
PY - 2022/1/1
Y1 - 2022/1/1
N2 - 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 cellassociated 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 cellassociated 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 progressionfree survival. CONCLUSIONS: This is the first study to describe a multicenter cohort of patients requiring ICU admission with cytokine release syndrome or immune effector cellassociated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy. Despite severe toxicities, organ support and in-hospital mortality were low in this patient population.
AB - 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 cellassociated 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 cellassociated 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 progressionfree survival. CONCLUSIONS: This is the first study to describe a multicenter cohort of patients requiring ICU admission with cytokine release syndrome or immune effector cellassociated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy. Despite severe toxicities, organ support and in-hospital mortality were low in this patient population.
KW - Chimeric antigen receptor T-cell
KW - Cytokine release syndrome
KW - Immune effector cell-associated neurotoxicity syndrome
KW - Intensive care unit
KW - Outcomes
UR - http://www.scopus.com/inward/record.url?scp=85122326648&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85122326648&partnerID=8YFLogxK
U2 - 10.1097/CCM.0000000000005149
DO - 10.1097/CCM.0000000000005149
M3 - Article
C2 - 34259446
AN - SCOPUS:85122326648
SN - 0090-3493
VL - 50
SP - 81
EP - 92
JO - Critical care medicine
JF - Critical care medicine
IS - 1
ER -