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

• Published in: Critical care medicine Vol. 50; no. 1; p. 81
• Main Authors: Gutierrez, Cristina, Brown, Anne Rain T, May, Heather P, Beitinjaneh, Amer, Stephens, R Scott, Rajendram, Prabalini, Nates, Joseph L, Pastores, Stephen M, Dharshan, Ananda, de Moraes, Alice Gallo, Hensley, Matthew K, Feng, Lei, Brudno, Jennifer N, Athale, Janhavi, Ghosh, Monalisa, Kochenderfer, James N, Arias, Alejandro S, Lin, Yi, McEvoy, Colleen, Mead, Elena, Westin, Jason, Kostelecky, Natalie, Mian, Agrima, Herr, Megan M
• Format: Journal Article
• Language: English
• Published: United States 01.01.2022
• Subjects: Adult; Aged; Biological Products - toxicity; Comorbidity; Critical Illness; Cytokine Release Syndrome - chemically induced; Cytokine Release Syndrome - mortality; Cytokine Release Syndrome - therapy; Female; Humans; Immunotherapy, Adoptive - adverse effects; Intensive Care Units - statistics & numerical data; Male; Middle Aged; Neurotoxicity Syndromes - etiology; Neurotoxicity Syndromes - mortality; Neurotoxicity Syndromes - therapy; Patient Acuity; Receptors, Chimeric Antigen; Retrospective Studies; Sociodemographic Factors; United States; United States
• ISSN: 1530-0293
• DOI: 10.1097/CCM.0000000000005149

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. Retrospective cohort study. Nine centers across the U.S. part of the chimeric antigen receptor-ICU initiative. Adult patients treated with chimeric antigen receptor T-cell therapy who required ICU admission between November 2017 and May 2019. Demographics, toxicities, specific interventions, and outcomes were collected. 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. 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.