Impact of adenovirus infection on the long-term cardiovascular and other outcomes following CAR T-cell therapy: A propensity-matched cohort study

Abstract Background: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematologic malignancies but is associated with profound immunosuppression, predisposing patients to opportunistic infections. Adenovirus infections, though uncommon, may have serious clinical consequences and their long-term impact on outcomes following CAR T-cell therapy remains poorly defined. This study aims to evaluate the long-term impact of adenovirus infection on the long-term outcomes in CAR T-cell recipients. Methods: We conducted a retrospective cohort study using a global real-world multicentric data to identify patients who received CAR T-cell therapy over the past 10 years. Patients were stratified based on the presence or absence of adenovirus infection and were propensity score matched 1:1 for age, race, BMI, and comorbidities, including hypertension, hypertensive heart disease with heart failure, diabetes mellitus, malnutrition, asthma, and emphysema. Patients record was tracked for 5 years and outcomes were recorded. The primary outcomes were all-cause 30-day mortality and hospital readmission. Risk differences, risk ratios (RR), and odds ratios (OR) with 95% confidence intervals (CIs) were calculated. Results: After propensity score matching, each cohort comprised 1,541 patients. Post-Propensity analysis revealed that patients with adenovirus infection had a higher 30-day mortality rate compared to those who did not experience infection (24.9% vs. 18.0%; risk difference: 6.9%, 95% CI: 4.1-9.8, p < 0.001). Kaplan-Meier analysis showed lower survival probability in the adenovirus cohort (54.5% vs. 59.9%). Additionally, patients in the adenovirus cohort had a higher risk of developing Acute Kidney Injury ( 23.8% vs. 17.2%; RR 1.38, 95% CI 1.19-1.59, p<0.001). In contrast, there was no significant difference in the readmission rate, onset of atrial fibrillation, new heart failure, myocardial infarction. Conclusions: Adenovirus infection following CAR T-cell therapy is associated with significantly increased mortality. These findings highlight the need for vigilant infection surveillance and early intervention in CAR T-cell recipients with adenovirus to improve outcomes in this high-risk population.