Six-Year Trends in ICU Admission, Management, and Outcomes of Chimeric Antigen Receptor T-Cell Patients in the ICU.

[OBJECTIVES] To evaluate evolving management, ICU admission, and outcomes for critically ill chimeric antigen receptor (CAR) T-cell patients over a 6-year period.

[DESIGN] Multicenter retrospective cohort study from January 2018 to September 2023.

[SETTING] Eight U.S. centers.

[PATIENTS] Adult CAR T-cell patients requiring ICU admission.

[INTERVENTIONS] None.

[METHODS] Summary statistics included mean, sd , median, and interquartile range (IQR). Fisher exact test or chi-square test were used to evaluate association between year treated and other categorical variables. Cochran-Armitage test was performed to assess significance of trends across years. Multivariable logistic regression was performed to assess covariates associated with mortality.

[MEASUREMENTS AND MAIN RESULTS] Demographics, toxicity management, ICU admission, support modalities, toxicity severity, and survival (ICU, hospital, and 3-mo) were compared year-to-year. From 2018 to 2023, 2238 patients received CAR T cells, with increasing number of patients treated yearly; 398 (17.8%) required ICU care. Of those admitted to the ICU, 66.1% were male, 89.2% had lymphoma, and median age was 64 years (53-71 yr). ICU admission rates declined from 38.5% (95% CI, 31.6-45.8%) in 2018 to 16.4% in 2023 (95% CI, 13.5-19.7%; p < 0.0001). Cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome was the reason for ICU admission in 87.9%. In 2023 vs. 2018, ICU patients were older (median, 65 yr [IQR, 55-73 yr] vs. 58 yr [48-67 yr]; p = 0.003) with higher comorbidity indices (4 [4-6] vs. 3 [2-4]; p = 0.005) and more severe toxicities (≥ grade 3: 90.1% vs. 69.9%; p = 0.004). Corticosteroid use for less severe toxicities (≤ grade 2 toxicity: 73.8% vs. 40.6%; p = 0.0001) and anakinra use (56% vs. 5.5%; p < 0.0001) increased throughout the years. Mortality from cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome remained low (5.5%). Age, Sequential Organ Failure Assessment greater than or equal to 10 at ICU admission, and ICU admission for noncytokine release/neurotoxicity syndrome reasons were associated with hospital mortality (odds ratios, 1.02 [95% CI, 1-1.04; p = 0.046], 4.69 [2.44-9.01; p < 0.0001], and 3.74 [1.91-7.3; p = 0.0001], respectively).

[CONCLUSIONS] ICU admission rates after CAR T-cell treatment are declining. Although ICU patients are older with higher severity of illness and toxicity grades, ICU mortality after CAR T-cell therapy remains low.