Novel autoantibodies panel predicted prognosis of diffuse large b‐cell lymphoma treated with r‐chop therapy

Introduction: DLBCL patients treated with R-CHOP regimen have prolonged survival, but 20%–40% of patients survive less than 5 years. Autoantibodies (AAbs) have the advantages of easy specimen acquisition and dynamic real-time monitoring. Blood-based autoantibodies have stratified lymphoma patients outcomes in previous studies, such as anti-ALK autoantibody titers were found to predict anaplastic large B-cell lymphoma (ALCL) recurrence risk stratification. This study was designed to find prognostic AAbs biomarkers for early progression, PFS, and OS in DLBCL patients treated with R-CHOP by utilizing a proteomic test based on autoantibodies. Patients and methods: Plasma samples from 325 DLBCL patients and FFPE samples from 37 DLBCL patients with biopsy confirmation were retrospectively collected between 2006 and 2020. All patients were previously untreated and collected before first-line R-CHOP and had complete clinical data. Patients were divided into relapse and non-relapse groups based on EFS24. There were three cohorts in this study. In the discovery phase, 20 samples were conducted comprehensively high-throughput protein microarray (∼20 K proteins, HuProtTM). In the verification phase, 181 samples were conducted low-density focused array (200 proteins). And in the validation phase, 135 samples were conducted for ELISA detection. Besides, exploratory analyses revealed the expression difference of prognostic AAbs target proteins in DLBCL FFPE samples. Results: Global autoantibody profiling of DLBCL patients were observed. Four autoantibodies were significantly different in relapse and non-relapse patients (p < 0.05) and associated with superior survival outcomes (PFS and OS) both in the verification phase (n = 181) and validation phase (n = 135). Based on the AUC for EFS24, 2 AAbs were chosen for the riskscore model conduction. 2 AAbs signature riskscore model was predictive of PFS with AUC of 0.72, 0.76 and 0.82 at 1, 3 and 5 years independent of IPI score in validation phase. Combining with the IPI score, 2 AAbs signature riskscore identified a more poor prognosis group (5-year PFS rate: 17.86%) versus IPI score high group (33.3%), a mediate group(56.49%) versus IPI score high_inter/low_inter group (46.3% and 48.2%) and a more favorable group (89%) versus IPI score low group (85.78%). Furthermore, 2 AAbs target proteins were also higher in DLBCL patients with superior outcomes (p < 0.05). Conclusions: We have demonstrated the extensive profiling of autoantibodies in DLBCL patients, and identified a novel prognostic AAbs panel and it can also contribute to improving the prognostic stratification ability of IPI score. Keywords: autoantibody, biomarker, diffuse large b-cell lymphoma, protein microarray Encore Abstract - previously submitted to regional or national meetings (up to <1000 attendees), EBMT 2023, AACR 2023, ASCO 2023, EHA 2023 The research was funded by: China National Major Project for New Drug Innovation (2017ZX09304015, 2019ZX09201-002) Keywords: aggressive B-cell non-Hodgkin lymphoma, diagnostic and prognostic biomarkers, risk models No conflicts of interests pertinent to the abstract.