Invasive fungal infections after CD19 chimeric antigen receptor T-cell therapy for B-cell lymphoma: a Lymphoma study association study from the DESCAR-T (Dispositif d'Enregistrement et Suivi des patients traités par CAR-T cells) registry.

[OBJECTIVES] To describe the landscape of invasive fungal infections (IFIs) after chimeric antigen receptor (CAR) T-cell therapy for B-cell malignancies from the French national DESCAR-T registry and evaluate risk factors associated with invasive fungal infections in this population.

[METHODS] We conducted a multicentre cohort study to describe the landscape of IFIs in adults with relapsed or refractory B-cell lymphoma treated with CD19 CAR T-cell therapy. Patients were identified through the French DESCAR-T registry. Clinical and biological data were collected retrospectively. Each IFI was classified according to the European Organization for Research and Treatment of Cancer (EORTC) criteria.

[RESULTS] Among the 1012 patients included in the registry from 2018 to 2022, 32 patients (3.1%) presented with proven (n = 14/32), probable (n = 12/32), or possible (n = 6/32) IFIs. The median time to onset was 29.5 days (IQR 16.5-79.5 days). The most frequent mould infection was invasive aspergillosis, occurring in 11 of 32 patients, whereas the most frequent yeast infection was candidemia occurring in 12 of 32 patients. The IFI-related mortality rate among infected patients was 21.8% (7/32 patients). Multivariate analysis identified several risk factors associated with IFIs: advanced age, number of prior lines of therapy, prior allogeneic haematopoietic cell transplantation, antiinterleukin-1 receptor antagonist treatments, and pre-IFI bacterial infection. The median overall survival of patients with IFIs was 6 months (95% CI, 1.0-20.6) compared with 25.4 months (95% CI, 20.5-32.0) in the noninfected population. The median progression-free survival of patients with IFIs was 3.2 (95% CI, 0.8-18.3) months compared with 5.8 months (95% CI, 4.5-6.7) in the noninfected population.

[CONCLUSIONS] Despite the low incidence of IFI in B-cell lymphoma patients treated with CD19 CAR T-cell therapy, the high infectious mortality underscore the need for individualized prophylaxis and rapid diagnosis for high-risk patients.