Novel Autoantibodies Biomarkers Panel to Prognosticate the Clinical Outcomes in Advanced-stage NSCLC Patients Receiving Anti PD-1/PD-L1 Immunotherapy. (28th October 2020)

• Record Type: Journal Article
• Authors: Tarhoni, I; Fhied, C; Borgia, J A; Fidler, M J; Batus, M; Bonomi, P
• Is Part Of: American journal of clinical pathology. Volume 154(2020)Supplement 1
• Page Start: S142
• Page End: S142
• Publication Date: 2020-10-28
• Subjects: Diagnosis, Laboratory -- Periodicals; Pathology -- Periodicals; 616.07
• DOI: 10.1093/ajcp/aqaa161.311
• Languages: English
• ISSNs: 0002-9173

Abstract

Abstract: Introduction/Objective: Lung cancer is the leading cause of cancer-related deaths worldwide, with a majority of cases detected at a non-resectable advanced stage. Current anti PD-1/-L1 therapy has reformed cancer treatment strategies with remarkable clinical outcomes in non-small cell lung cancer (NSCLC). However, the overall response rate is still marginal, demonstrating the need for biomarkers predictive of response. The objective of this study is to develop a serum based panel to prognosticate clinical response in advanced NSCLC patients receiving anti PD-1/-L1 therapy. Methods: Pooled sera from two response groups (Poor response, n=20, overall survival < 12 months; Good response, n=20, overall survival > 12 months) were evaluated via the HuProt™ Human Proteome Microarray (CDI laboratories, Baltimore, MD) to identify expressed neoantigens. Recombinant proteins representative to identified neoantigens along with their corresponding antibodies, were commercially acquired to develop a robust 13-plex bead- based immunoassay to evaluate the autoantibodies in pretreatment sera from 125 advanced-stage NSCLC patients. Finally, levels of autoantibodies were correlated to clinical outcome, including progression free survival (PFS), overall survival (OS) and grade III adverse events. Results: Low baseline levels of ZNF695, MCM4, PRMT2, FGD3, GTF2A1, GLUL, CDCA3, ZNF277, GARS, GBP2, UBL7, and ASNA1 autoantibodies were found to be associated with a longer PFS (all p-values < 0.01), whereas increased levels were associated with a poor PFS outcome (0.06, HR=0.66, 95% CI). Low levels of ZNF695, MCM4, PRMT2, FGD3, GARS, GBP2, and UBL7 autoantibodies were associated with favorable OS (all p-values < 0.01). Conclusion: In this study we demonstrated that serum autoantibodies have great promise to serve as a prognostic tool for immunotherapy response. We successfully developed a high performance multiplexed serum based assay to evaluate autoantibodies in an advanced NSCLC patients receiving anti PD-1/-L1 therapy.