Introduction: Infectious complications are a significant cause of morbidity and mortality after CAR T-cell therapy. We assessed the risk factors and outcomes of patients who developed infections during ICU admission within 30 days of CAR T-cell infusion. Methods: Retrospective cohort of CAR T-cell recipients requiring ICU admission at 8 US centers (1/2018-9/2023), excluding patients with a primary diagnosis of sepsis. Data collected included demographics, malignancy type, CAR product, SOFA score, CRS and ICANS toxicity grade, immunosuppressive therapy received and infection type. Summary statistics include median (IQR) for continuous variables; numbers and percentages for categorical variables. Chi-square and Wilcoxon rank sum tests were used to evaluate differences between patients with and without infections. Results: 382 CAR T-cell recipients were admitted to the ICU; 86 (22.5%) developed infections (i.e., positive cultures). Fifty-five patients (64%) had bacterial infections, 25 (29%) viral and 11 (13%) fungal; 9 (10%) patients had >1 type of infection. Age, malignancy, and CAR product administered were similar in patients with and without infection. Patients with infectious complications were more likely to have Grade ≥3 CRS or ICANS (41% vs. 25%, p=0.006; 76% vs. 62%, p=0.02; respectively) or immune effector cell-related hemophagocytic lymphohistiocytosis (18% vs. 3.6%; p=0.0004). SOFA score was 6 and 5 in patients with and without infections, respectively (p=0.0007) The number of patients who received steroids and tocilizumab was similar, but patients with infections were more likely to have received anakinra (44% vs. 30%, p=0.01), higher steroid dose (median (IQR) 2026 mg (853-4656) vs.1227 mg (560-3253); p=0.02) or other immunosuppressants for refractory toxicities (16% vs. 4%; p=0.0001). Hospital mortality was higher in patients with infections compared to those without infections (41% vs. 15%; p< 0.0001). Conclusions: 1 in 5 CAR T-cell recipients admitted to the ICU developed infections and had higher mortality rates compared to those without infections. These data may reflect an added risk of stacking multiple immunosuppressive drugs for treating high-grade CAR T-cell toxicities. Improved strategies are needed to prevent and manage infections for those at high risk to improve patient outcomes.
McEvoy et al. (Sun,) studied this question.