P1131: serum triglyceride and apolipoprotein a1 as biomarkers for extranodal natural killer/t cell lymphoma (enktl): a multicenter study

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: With the application of pegaspargase (Asp) and early intervention with radiotherapy, the clinical outcome of extranodal NK/T cell lymphoma (ENKTL) has been improved significantly. However, some patients resistant to Asp-based chemotherapy suffered poorer survival. Therefore, reliable and convenient biomarkers become more indispensable to individualized therapy. With the advances in lipidomics, lipid metabolism reprogramming is currently emerging as a disorder associated with neoplastic process, drawing more attention to the role of lipid metabolism in ENKTL. Aims: We compared the lipid profiles between ENKTL patients and healthy controls and analyzed the application value of serum lipid in ENKTL. Methods: We retrospectively analyzed 1017 ENKTL patients with available clinical data between December 2003 and August 2021. Demographics and serum lipid data of 500 healthy controls were reviewed. The median values at baseline were selected as the cutoff values for serum lipid. Kaplan–Meier curves were plotted, while differences in survival were assessed using the log-rank test. Results: The baseline serum levels of high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and apolipoprotein A1 (ApoA1) were lower, while the levels of triglyceride (TG) was higher in ENKTL patients than those in age- and gender-matched healthy controls (all p<0.001). Besides conventional predictive factors, baseline serum TG (PFS: p=0.017; OS: p=0.018) and ApoA1 (PFS: p=0.007; OS: p=0.002) were identified as independent prognostic factors. Among patients with high levels of TG (or low levels of ApoA1) at baseline, those who exhibited objective responses had a significant serum TG decrease (or ApoA1 increase) after treatment (all p<0.001). However, no significant change of TG or ApoA1 (p=0.175 and 0.734, respectively) was observed in patients without satisfactory response. Compared with baseline levels, further increased levels of TG and decreased levels of ApoA1 after first-line treatment were associated with significantly shorter PFS (all p<0.001) and OS (all p< 0.001, Figure A-B). We developed and validated a pre-treatment nomogram containing TG and ApoA1 at baseline and a post-treatment nomogram containing serum lipid at best response (Figure C-D). Post-treatment nomogram demonstrated higher prognostic accuracy for OS prediction when compared with the prognostic index of natural killer lymphoma (PINK) and pre-treatment nomogram, which corresponded to the C-indexes (in training cohort: 0.743, 0.662, and 0.686, respectively; in validation cohort: 0.754, 0.655, and 0.674, respectively) and AUCs (in training cohort: 0.81, 0.72, and 0.74, respectively; in validation cohort: 0.82, 0.70, and 0.73, respectively) for 5-years survival prediction. Subgroup analysis showed that Asp-containing regimens was associated with significant survival benefits among patients with low levels of LDL-C and high levels of HDL-C and ApoA1 at baseline (all p<0.001). Furthermore, the comprehensive transcriptome analysis provided evidence for intratumoral lipid metabolic disorders and dysregulated classical tumor-related signaling pathways, including NOTCH and MAPK, among patients with high levels of TG (or low levels of ApoA1) at baseline (Figure E-F).Summary/Conclusion: This study suggests that ENKTL is accompanied by dyslipidemia. Baseline levels and change trends of TG and ApoA1 could contribute to risk stratification, disease status monitoring and treatment outcome prediction. Patients with dyslipidemia also have intratumoral lipid metabolic disorders and dysregulated classical tumor-related signaling pathway Keywords: Extranodal lymphoma, Non-Hodgkin’s lymphoma