Persistent and pathogen-specific infection risk during long-term survivorship after CD19 CAR-T: An Australian multi-centre cohort study
- Author(s)
- Reynolds, GK; Dowling, MR; Belbachir, S; Perera, N; Li, J; Vanguru, V; Teh, BW; Anderson, MA; Barraclough, A; Tam, CS; Ho, PJ; Harrison, SJ; Henden, AS; Thursky, KA; Slavin, MA;
- Journal Title
- Clinical Microbiology and Infection
- Publication Type
- Jun 24
- Abstract
- OBJECTIVES: Infection remains the leading cause of non-relapse mortality after CD19 CAR-T therapy. However, the aetiology and risk of late infections, particularly beyond one year post infusion, remain poorly defined. METHODS: This national multicentre retrospective cohort study included adults receiving standard-of-care CD19 CAR-T for aggressive lymphoma across five Australian centres between 2019-2023, with follow-up to March 2025. Infections were classified as microbiologically confirmed or clinically defined using consensus definitions. Outcomes included infection incidence, timing, microbiological aetiology, and pathogen-specific risk factors. Cause-specific Cox proportional hazards regression, with death as a competing risk, evaluated risks for microbiologically confirmed infections and early (day 0-30), medium (day 31-365) and late (≥365 days) infection events, with Firth regression used for sensitivity analyses. RESULTS: Among 291 patients, 49.5% (144/291) experienced ≥1 infection (249 events); 36% (106/291) developed a severe infection (grade ≥3 CTCAE) and 5% (16/291) suffered a fatal infection. Of 146 patients evaluable after 1 year (median follow-up 600 days, IQR 420-900), 40% experienced a late infection (57/146) and 18% (27/146) a severe late infection. Respiratory viral infections (RVIs) were the most common late infections (37/89 events), and the proportion of severe RVIs did not decline over time. Early infection (OR 2.96, 95% CI 1.32-6.87, p=0.009) was associated with infection between days 31-365. No predictors of infections beyond one year were identified. Fungal infections were uncommon (6% of cohort, 17/291) but showed a distinct risk profile. Cumulative dexamethasone exposure and antecedent bacterial infection were associated with invasive fungal disease in multivariable analysis (p<0.05). A threshold of ≥56 mg dexamethasone equivalent within the first 28 days predicted fungal risk (95% CI 1.6-27.1; AUC 0.71; p=0.015). CONCLUSION: Late infections were common and clinically significant, with RVIs remaining a major source of morbidity. Fungal infection risk was associated with corticosteroid exposure extending beyond 6 months, supporting ongoing infection surveillance and prevention strategies beyond the first post infusion year.
- Publisher
- Elsevier
- Research Division(s)
- Blood Cells and Blood Cancer
- PubMed ID
- 42341925
- Publisher's Version
- https://doi.org/10.1016/j.cmi.2026.06.019
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-06-26 08:17:25
Last Modified: 2026-06-26 08:20:37