Timeline and outcomes of viral and fungal infections after chimeric antigen receptor T-cell therapy: a large database analysis

This large database analysis aims to describe the incidence, timeline, and risk factors for viral and fungal infections after chimeric antigen receptor (CAR) T-cell therapy. We queried a global research network database, TriNetX, for patients who received CAR T-cell therapy, who were identified and followed for the development of viral and fungal infections. Baseline demographic, oncologic history, laboratory data and medication histories were collected. We evaluated risk factors for respiratory viral infections (RVIs), herpesvirus, fungal infections and mortality using Cox regression. A total of 2256 patients who received CAR T-cell therapy were included, 1867 (82.7%) were CD19-targeted and 400 (17.7%) were B-cell maturation antigen-targeted. After CAR T-cell infusion, RVIs were the most prevalent (23.3%) with a median onset of 160 days (interquartile range [IQR]: 52–348 days), whereas herpesvirus and fungal infections were less frequent, occurring in 13.6% and 11.4% of cases with median onsets of 71 (IQR, 18–252) and 73 days (IQR, 14–236 days), respectively. On multivariable Cox regression, independent predictors of RVI included acute lymphoblastic leukaemia (hazard ratio [HR], 1.61), prior haematopoietic cell transplant (HCT; HR, 1.29), cytokine release syndrome (HR, 1.41), hemophagocytic lymphohistiocytosis (HR, 1.96) and glucocorticoids (HR, 3.37). Prior HCT (HR, 2.00), hypogammaglobulinemia (HR, 1.51), immune effector cell-associated neurotoxicity syndrome (HR, 1.52) and hemophagocytic lymphohistiocytosis (HR, 1.99) were associated with a higher risk of herpesviruses. Independent predictors of fungal infections included prior HCT (HR, 1.59), cytokine release syndrome (HR, 1.58) and hypogammaglobulinemia (HR, 1.40). Idecabtagene vicleucel was associated with a lower risk of herpesvirus and fungal infections (HR, 0.39 and 0.44, respectively). In a large cohort of CAR T-cell therapy recipients, RVIs were the most common but occurred later, whereas herpesvirus and fungal infections were less frequent but occurred earlier. Prospective studies investigating prophylaxis and pre-emptive monitoring strategies are needed in this population.