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

Abstract

To evaluate evolving management, ICU admission, and outcomes for critically ill chimeric antigen receptor (CAR) T-cell patients over a 6-year period. Multicenter retrospective cohort study from January 2018 to September 2023. Eight U.S. centers. Adult CAR T-cell patients requiring ICU admission. None. 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. 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). 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.