Event-Free Survival at 12 Months Predicts Long-Term Outcomes in DLBCL Patients Receiving CAR-T Therapy

Aditya Ravindra; Bradley T. Loeffler; Christopher Sun Strouse; Umar Farooq

doi:10.1016/j.jtct.2025.12.550

Introduction Event-free survival (EFS) 24 months after frontline chemoimmunotherapy and progression-free survival (PFS) at 24 months after autologous stem cell transplant are established prognostic markers of overall survival (OS) in diffuse large B-cell lymphoma (DLBCL). A similar benchmark for CAR-T therapy has not been defined. In ZUMA-1, patients achieving 12-month EFS (EFS12) after axi-cel had markedly higher 5-year OS (90.9% vs. 5.3%). This study evaluates whether patients reaching EFS12 post-CAR-T have comparable lymphoma-related and unrelated mortality, supporting EFS12 as a surrogate for OS in this setting. Objectives Recognize the prognostic value of EFS12 as a predictor of long-term survival after CAR-T in DLBCL • Understand that baseline clinical/treatment features did not distinguish EFS12 achievers from non-achievers. • Appreciate that EFS12 patients show durable remissions, with prolonged PFS and high 5-year survival. Methods This retrospective, single-center study evaluated DLBCL patients treated with standard-of-care CAR-T at the University of Iowa. Patients were grouped by achievement of EFS12; none were lost to follow-up at 1 year. Baseline clinical, disease, and treatment characteristics were compared using chi-square or Fisher's exact tests for categorical variables and Kruskal-Wallis tests for continuous variables. After 12 months of follow-up, PFS was estimated with Kaplan-Meier curves. Time-to-event was measured from 12 months post–CAR-T to progression or death, with censoring at last assessment. Results Among 69 patients with DLBCL treated with standard-of-care CAR-T, most had advanced-stage disease (85.5%), an IPI score of 3 (31.9%), and two prior therapy lines (63.8%). R-CHOP was the predominant first-line regimen (62.3%), and 89.9% had not undergone autologous stem cell transplant. Axi-cel was the most frequently used CAR-T product (85.5%). EFS12 was achieved in 23 patients (33.3%). No significant differences in demographic and clinical features were observed between the EFS12 and non-EFS12 groups (p>0.05). The majority of EFS12 patients had advanced-stage disease (82.6%), median IPI of 3, and median two prior therapies. At 31.1-month median follow-up, median PFS was not reached; 68% were progression-free at 5 years with 2 lymphoma- and 2 prior therapy-related deaths (myelodysplastic syndrome). Six patients had ≥2 infections with a mean IgG of 554.7 in the EFS12 population. Conclusion Patients with DLBCL who achieved EFS12 post-CAR-T represented one-third of the cohort and shared similar baseline characteristics with the overall population. Despite the absence of distinguishing clinical or treatment factors, this subgroup demonstrated favorable long-term outcomes, with a median follow-up exceeding 30 months and a 5-year PFS of 68%, underscoring the prognostic significance of reaching the EFS12 milestone after CAR-T therapy.

Event-Free Survival at 12 Months Predicts Long-Term Outcomes in DLBCL Patients Receiving CAR-T Therapy

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