Survival outcomes of Epstein-Barr virus-positive diffuse large B-cell lymphoma, not otherwise specified: Results from Latin American and United States cohorts.

7045 Background: Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+ DLBCL), not otherwise specified, is rare in North America and Europe (2–4%) but prevalent in Latin America (LATAM, 7–14%). Most studies are limited by single-center designs, small cohorts, short follow-up, and infrequent rituximab use. Prognostic systems like the International Prognostic Index (IPI) are widely used, yet their predictive power in EBV+ DLBCL remains unclear. Additionally, the optimal threshold for EBV-encoded RNA (EBER) positivity remains controversial, with cutoffs ranging from ≥20% to ≥80%. This study aimed to characterize clinical outcomes and evaluate prognostic scores and EBER thresholds in LATAM patients treated with chemoimmunotherapy, contrasted with a U.S.-based cohort. Methods: This multicenter retrospective cohort study included patients diagnosed with EBV+ DLBCL from 2002–2020 in five LATAM countries (GELL registry) and a two U.S. centers (2008–2023). EBV positivity was defined per institutional EBER standards. Patients managed without anti-CD20 antibodies were excluded. Outcomes (overall survival [OS] and progression-free survival [PFS]) were assessed using Kaplan-Meier analysis, log-rank tests, and Cox regression. Prognostic systems (IPI, NCCN-IPI, R-IPI, Oyama score) were evaluated using C-indices. Results: In the LATAM cohort (n=139), median age was 58 years, 71% had advanced-stage (stage III-IV) disease, and 90% received R-CHOP. In the U.S. cohort (n=136), median age was 67 years, 74% had advanced-stage disease, and 74% received R-CHOP. In the LATAM cohort, with a median follow-up of 61 months (95% CI=53-68), 43 deaths were observed. The 5-year OS and PFS rates were 63% (95% CI=54-73%) and 50% (95% CI=41-60%), respectively. In the US cohort, with a median follow-up of 54 months (95% CI=45-66), 52 deaths were observed. The 5-year OS and PFS rates was 54% (95% CI=45-65%), and 41% (95% CI=32-52%), respectively. All evaluated prognostic scores had a similar performance in the LATAM (OS: C-index range 0.595-0.674; PFS: C-index range 0.553-0.633) and US (OS: C-index range 0.679-0.744; PFS: C-index range 0.701-0.782) cohorts. EBER test ≥80% was associated with mortality in the US cohort (adjusted HR=2.76, 95% CI=1.53-5.00). Conclusions: To the best of our knowledge this is one of the largest studies on EBV+ DLBCL. This study highlights comparable survival outcomes for EBV+ DLBCL in LATAM and the U.S. with chemoimmunotherapy, supporting its use in the management of this rare entity. Prognostic systems show variable performance across regions, emphasizing the need for further validation in EBV+ DLBCL populations. Variability in EBER thresholds underscores the need for standardized diagnostic criteria to optimize prognostication and treatment.