Lymphoma Study Association

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. 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. 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. 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.

Genome-wide association studies (GWAS) have identified germline genetic variants for follicular lymphoma (FL) susceptibility. We conducted a GWAS of prognosis in FL patients to identify genetic predictors of event-free survival (EFS) as well as failure within the first 24 months after treatment initiation (EFS24) using patients treated with rituximab-based immunochemotherapy from three clinical trials and one prospective observational study (N = 1054). Statistical approaches consisted of a pooled GWAS of the four cohorts and a leave-one-cohort-out (LOCO) strategy to identify robust findings that replicated across the four cohorts. The top SNPs for EFS and EFS24 were marked by rs72625024 at 3q27.3 near FETUB and HRG (P = 9.37 × 10-8) and rs114695031 at 14q32.13 near TCL6 (P = 1.93 × 10-8), respectively. These two loci, which were discovered and validated in all 4 LOCO rounds, map near long-non-coding RNAs with putative tumor suppressor functions. Our results pinpoint potential novel biology and the contribution of host genetics to prognosis in FL.