P1189: endothelial activation and stress index is an independent prognostic factor of diffuse large b-cell lymphoma treated with standard immunochemotherapy

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: The natural history of diffuse large B-cell lymphoma (DLBCL) is heterogeneous. Several prognostic models have been investigated to predict treatment outcomes of patients with DLBCL. Endothelial activation and stress index (EASIX) is a surrogate of endothelial dysfunction as noted in various inflammatory states including malignancy. The elevated EASIX score was demonstrated to be associated with inferior outcomes in patients with multiple myeloma, low-risk myelodysplastic syndrome and patients treated with cell-based immunotherapy. However, the implication of EASIX on the prognosis of DLBCL is limited and warrants exploration. Aims: To evaluate the prognostic implication of EASIX score in patients with DLBCL treated with immunochemotherapy. Methods: This is a single center study enrolling adult patients with newly diagnosed DLBCL receiving immunochemotherapy at the King Chulalongkorn Memorial Hospital between January 2013 and December 2022. Clinicopathological data were abstracted from the electronic medical record. EASIX score was calculated using serum creatinine, lactate dehydrogenase and platelet according to the original report by Luft and colleagues. The optimal cutoff of EASIX for survival outcomes was determined by the time-dependent receiver operating characteristic curves (ROC). Relevant survival endpoints including progression free survival (PFS) and overall survival (OS) were analyzed using Kaplan Meier Estimate. Cox proportional hazards analysis was performed to explore the impact of EASIX on survival outcomes. Results: A total of 323 patients with newly diagnosed DLBCL were included in the study. The median EASIX score was 1.00 (range, 0.17-136.94). Using the ROC analysis, the optimal EASIX cutoff was 1.07 stratifying patients into the low EASIX (n=174, 53.9%) and high EASIX (n=149, 46.1%) groups (Figure 1). In the high EASIX group, there was a significantly higher proportion of patients with advanced stage, bulky disease, and impaired performance status. Patients with high EASIX score significantly presented with higher risk diseases as determined by the International Prognostic Index (IPI). After the receipt of treatment, the interim EASIX score after 4 cycles of treatment was significantly lower than the pre-treatment values, however, the C4-EASIX was not associated with outcomes. Of 290 evaluable patients, the overall response rate (ORR) of the entire cohort was 91.7% (complete remission, CR 67.9%). Patients with high EASIX score had a significantly lower CR than those with low EASIX score (89.6% vs. 73.8%, p<0.001). After a median follow up of 34.6 months, 79 patients (24.4%) relapsed, and 96 patients (29.7%) had died. Patients with high EASIX score had a significantly inferior PFS (2-year PFS 53.4% vs. 81.5%, p<0.001) and OS (2-year OS 64.4% vs. 88.7%, p<0.001) compared to patients with low EASIX score (Figure 2 and 3). Multivariate analysis revealed that older age, bulky disease, impaired performance status, and high EASIX score were associated with an unfavorable OS. Summary/Conclusion: In patients with DLBCL, a high EASIX score is an independent prognostic factor of an unfavorable survival outcome. Further studies in larger patient cohorts are warranted to validate its prognostic implication as a simple tool to identify high-risk patients.Keywords: Diffuse large B cell lymphoma, Endothelial dysfunction, Outcome, Prognosis