Abstract 5753: Comprehensive analysis and potential clinical applications of immunotherapy-related biomarkers in Chinese patients with pancreatic adenocarcinoma
Authors: Wang Yu , Xu Yantian , Feng Alei , Wen Qiang , Shi Xiaoliang , Zhang Shanshan , Pang Fei 
Published: June 2022

Abstract
Background: Pancreatic adenocarcinoma (PAC) is a malignant tumor with less than 5% of 5-year overall survival. Although immunotherapy has shown excellent and lasting efficacy in many solid tumors, immunomonotherapy is ineffective in PAC. The combinations of immune checkpoint inhibitors (ICIs) with radiotherapy/chemotherapy has shown encouraging results. Identifying predictive biomarkers is of great sense for PAC patients to benefit from immunotherapy.
Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matched blood samples of 83 Chinese PAC patients were collected from Shandong Provincial Hospital Affiliated to Shandong First Medical University. Next-generation sequencing (NGS) of targeted-450 cancer genes was performed in OrigiMed (Shanghai, China), a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Genomic alterations, tumor mutational burden (TMB), and microsatellite instability (MSI) were assayed. PD-L1 expression was determined using Combined Positive Score (CPS).
Results: A total of 83 PAC patients were enrolled in this cohort, including 50 (60.2%) males and 33 (39.8%) females. Among them, 79.5% (66/83) and 20.5% (17/83) were primary and metastatic lesions, respectively. The most common mutant genes were KRAS (84.3%, 70/83), TP53 (75.9%, 63/83), CDKN2A (27.7%, 23/83), SMAD4 (26.5%, 22/83) and ARID1A (12.0%, 10/83). In addition, some gene alterations associated with immune hyperprogression (HP) were detected in 9.6% (8/83) patients, including 11q13 amp (2.4%, 2/83), and CDKN2A/B gene loss (7.2%, 6/83). There are 32 (38.6%) PD-L1 positive patients, including 25 patients with CPS 1-10 and 7 patients with CPS≥20. We found that SPTA1 mutations were specifically detected in PD-L1 positive group, while OBSCN and ATM mutations were specifically detected in PD-L1 negative group. The median TMB value was 3.3 muts/Mb and only 4 (4.8%) patients had TMB-values higher than 10 muts/Mb (TMB-H). There are 3 patients (3.6%) showed MSI-H. Interestingly, all 3 MSI-H patients were TMB-H, and 2 of them also showed PD-L1 positive without any HP related mutations. Both patients received immunotherapy and were benefited for more than 11 months, including one of whom had received immunomonotherapy.
Conclusions: We described the characteristics of TMB, MSI and PD-L1 expression in Chinese patients with PAC. In the absence of HP related mutations, comprehensive consideration of TMB, MSI and PD-L1 status may guide PAC immunotherapy and benefit PAC patients.
Citation Format: Yu Wang, Yantian Xu, Alei Feng, Qiang Wen, Xiaoliang Shi, Shanshan Zhang, Fei Pang. Comprehensive analysis and potential clinical applications of immunotherapy-related biomarkers in Chinese patients with pancreatic adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5753.