Persistent and pathogen-specific infection risk during long-term survivorship after CD19 chimeric antigen receptor T-cell therapy: an Australian multicentre cohort study

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

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;
Details: Publication Year 2026-11,Volume 32,Issue #11,Page 1864-1872
Journal Title: Clinical Microbiology and Infection
Publication Type: Jun 24
Abstract: OBJECTIVES: Infection remains the leading cause of nonrelapse mortality after CD19 chimeric antigen receptor T-cell (CAR-T) therapy. However, the aetiology and risk of late infections, particularly beyond 1 year after 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 and 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 Common Terminology Criteria for Adverse Events [CTCAE] and 5% (16/291) suffered a fatal infection. Of 146 patients evaluable after 1 year (median follow-up, 600 days; interquartile range, 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 and 365. No predictors of infections beyond 1 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; area under the curve, 0.71; p 0.015). CONCLUSIONS: 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 postinfusion year.
Publisher: Elsevier
Keywords: Humans; Female; Australia/epidemiology; Retrospective Studies; Middle Aged; Male; Aged; Risk Factors; Adult; *Immunotherapy, Adoptive/adverse effects; *Antigens, CD19/immunology; *Persistent Infection/epidemiology/etiology; *Receptors, Chimeric Antigen; Lymphoma/therapy; Incidence; Bacterial infection; Cellular therapy; Chimeric antigen receptor T-cell therapy; Infection; Invasive fungal infection; Lymphoma; Respiratory viruses / respiratory viral infection
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: 2026-11-03 08:46:05