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

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.

• Authors: Cristina Gutierrez, Anne Rain T Brown, Heather P May, Amer Beitinjaneh, R Scott Stephens, Prabalini Rajendram, Joseph L Nates, Stephen M Pastores, Ananda Dharshan, Alice Gallo de Moraes, Matthew K Hensley, Lei Feng, Jennifer N Brudno, Janhavi Athale, Monalisa Ghosh, James N Kochenderfer, Alejandro S Arias, Yi Lin, Colleen McEvoy, Elena Mead, Jason Westin, Natalie Kostelecky, Agrima Mian, Megan M Herr
• Journal: Critical care medicine (Crit Care Med) Vol. 50 Issue 1 Pg. 81-92 (01 01 2022) ISSN: 1530-0293 [Electronic] United States
• PMID: 34259446 (Publication Type: Journal Article, Multicenter Study)
• Copyright: Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Chemical References

• Biological Products
• Receptors, Chimeric Antigen
• axicabtagene ciloleucel

Topics

• Adult
• Aged
• Biological Products (toxicity)
• Comorbidity
• Critical Illness
• Cytokine Release Syndrome (chemically induced, mortality, therapy)
• Female
• Humans
• Immunotherapy, Adoptive (adverse effects)
• Intensive Care Units (statistics & numerical data)
• Male
• Middle Aged
• Neurotoxicity Syndromes (etiology, mortality, therapy)
• Patient Acuity
• Receptors, Chimeric Antigen
• Retrospective Studies
• Sociodemographic Factors
• United States