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

Area of Science:

• Oncology
• Immunology
• Critical Care Medicine

Background:

• Chimeric antigen receptor (CAR) T-cell therapy has revolutionized cancer treatment but can lead to severe immune-related toxicities.
• Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are significant adverse events requiring intensive care.
• Limited data exists on the epidemiology and outcomes of patients with these toxicities admitted to the ICU.

Purpose of the Study:

• To describe the characteristics, treatments, and outcomes of adult patients admitted to the intensive care unit (ICU) following CAR T-cell therapy due to CRS or ICANS.
• To identify factors influencing patient outcomes in this critical care setting.

Main Methods:

• A retrospective cohort study was conducted across nine US centers participating in the CAR-ICU initiative.
• Data were collected on 105 adult patients admitted to the ICU between November 2017 and May 2019 after receiving CAR T-cell therapy (axicabtagene ciloleucel).
• Information gathered included demographics, toxicity profiles, interventions, and clinical outcomes.

Main Results:

• Most patients (66.7%) presented with grade 3-4 toxicities upon ICU admission, with ICANS being more frequent (64%) than CRS (15.2%).
• During ICU stay, CRS occurred in 77.1% and ICANS in 84.8% of patients, with 61.9% experiencing both. Despite severe toxicities, requirements for vasopressors (18.1%), mechanical ventilation (10.5%), and dialysis (2.9%) were uncommon.
• ICU mortality was 8.6%, with only three deaths directly attributed to CRS or ICANS. Neurological complications like seizures and cerebral edema were prevalent. Median overall survival was 10.4 months.

Conclusions:

• This multicenter study provides the first comprehensive description of patients requiring ICU admission for CRS or ICANS post-CAR T-cell therapy.
• Despite the severity of these immune-related adverse events, intensive care management resulted in low organ support utilization and in-hospital mortality.
• Higher cumulative corticosteroid doses were associated with decreased overall and progression-free survival, suggesting a potential impact on long-term efficacy.