Time from diagnosis to CAR T as a predictor of outcomes in transformed follicular lymphoma: A CIBMTR real-world analysis.

Abstract

e19016 Background: CD19-directed CAR T-cell therapy is effective in relapsed/refractory transformed follicular lymphoma (tFL), but the prognostic impact of the interval from diagnosis to CAR T infusion remains unclear. We evaluated the association between time from initial diagnosis to CAR T therapy and clinical outcomes in a large real-world cohort. Methods: This retrospective multicenter study utilized the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, based on the P-6131 dataset by Thiruvengadam et al. Adult tFL patients who received CAR T-cell therapy were included. Patients stratified based on the interval from initial lymphoma diagnosis to CAR T infusion as <24 months versus ≥24 months. Survival outcomes were estimated using the Kaplan–Meier method. Cox proportional hazards regression models were used to calculate crude and adjusted hazard ratios (HR) with 95% confidence intervals (CI). Logistic regression was used to assess associations with binary outcomes. Statistical analyses were performed using SPSS, with p-values <0.05 considered statistically significant. Results: Among 923 tFL patients treated with CAR T therapy, the mean interval from initial diagnosis to CAR T infusion was 22.8 months (SD 34.6). A total of 706 patients (76.5%) underwent CAR T within 24 months of diagnosis, while 217 (23.5%) received CAR T at ≥24 months. Patients with a ≥24-month interval demonstrated significantly improved outcomes. Median overall survival (OS) was 42.45 months in the ≥24-month group versus 29.14 months in the <24-month group (p = 0.004). While the crude OS benefit was significant (HR 0.691, 95% CI 0.537–0.887; p = 0.004), this association was insignificant after adjustment for disease and treatment characteristics (HR 0.765, 95% CI 0.538–1.089; p = 0.137).Progression-free survival (PFS) was markedly longer in the ≥24-month group, with median PFS of 29.44 months compared with 8.85 months in the <24-month group (p <0.001). This difference remained significant after multivariable adjustment (adjusted HR 0.696, 95% CI 0.514–0.943; p = 0.019).At 2 years, relapse incidence was significantly lower in patients with a ≥24-month interval (33.0% vs 49.9%; OR 0.503, 95% CI 0.363–0.697; p <0.001). Two-year treatment-related mortality was similar between groups (11.1% vs 8.65%; OR 1.301, 95% CI 0.79–2.143; p = 0.301). Rates of cytokine release syndrome (OR 1.026, 95% CI 0.712–1.476; p = 0.892), and ICANS (OR 1.385, 95% CI 0.991–1.936; p = 0.056) were comparable. Conclusions: An interval ≥24 months from diagnosis to CAR T was associated with superior PFS and reduced relapse in tFL. Early progression likely reflects aggressive, CAR T–resistant biology, underscoring the need for risk-adapted and novel strategies for early-transforming disease.