Cytomegalovirus Infection and Clinical Outcomes in Hospitalized Chimeric Antigen Receptor T-Cell Therapy Recipients

BACKGROUND: Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the management of hematologic malignancies but is associated with significant toxicities, including opportunistic infections such as cytomegalovirus (CMV). Limited evidence exists regarding the clinical impact of CMV in CAR-T recipients. This study evaluated outcomes associated with CMV infection in this population. METHODS: A retrospective cohort study was conducted using the 2021 Healthcare Cost and Utilization Project-National Readmissions Database (HCUP-NRD). Adult patients hospitalized for CAR-T therapy for multiple myeloma, non-Hodgkin lymphoma, or acute leukemia were included. Propensity score matching was applied to balance baseline characteristics, and weighted analyses were conducted in R software (R Foundation for Statistical Computing, Vienna, Austria) to compare outcomes between CMV-positive and CMV-negative groups. RESULTS: Among 1,806 hospitalizations, CMV infection was identified in 2.2% of patients during the index admission. In the matched cohort, in-hospital mortality in the CMV group compared with non-CMV patients (10.3% vs. 2.6%; risk ratio (RR) 3.9, 95% CI: 0.46-33.3; p = 0.36). CMV infection was associated with significantly longer length of stay (41.5 vs. 15.9 days; adjusted ratio 1.67, 95% CI: 1.27-2.19; p < 0.01) and increased risk of encephalopathy (RR 13.21, 95% CI: 1.66-105.2; p = 0.015). Other complications, including cytokine release syndrome, tumor lysis syndrome, acute kidney injury, and transfusion requirements, did not differ significantly. At three months post-CAR-T, the cumulative incidence of patients hospitalized with CMV infection was 4.2%. Three-month mortality was significantly higher in CMV patients compared with non-CMV patients (15.8% vs. 2.5%; RR 6.32, 95% CI: 1.46-27.3; p = 0.004). CONCLUSION: CMV infection in CAR-T recipients is associated with increased in-hospital mortality, extended hospital stays, and a higher risk of encephalopathy. These findings underscore the importance of vigilant monitoring and early management of CMV in this high-risk population.