Abstract P48: MULTIMODAL DATA INTEGRATION FOR A PAN-CANCER ASIAN COHORT OF EXCEPTIONAL RESPONDERS AND HYPER-PROGRESSORS TO IMMUNOTHERAPY HIGHLIGHTS UTILITY OF BIOMARKERS

Abstract

While cancer immunotherapy has become an important treatment option, heterogenous responses to immune checkpoint inhibitor (ICI) treatment across diverse cancer types remain a significant clinical challenge. The SUPER (Singapore Translational Cancer Consortium (STCC) Unified PD1/PD-L1 Evaluation of Response) study aims to develop and validate a combined assay of predictive biomarkers for patient response to ICI treatment. A cohort of 100 exceptional responder and 100 hyper-progressor patients in Singapore spanning different cancer types were identified and a series of assays were performed using the patients’ pre-ICI treatment tumor samples. As the research data integration team building the STCC Integrated Research Data Hub in collaboration with STCC and Genome Institute of Singapore, we have developed pipelines to collect, curate, process, analyze and visualize datasets for this cohort, as they become available. Whole exome and RNA sequencing (WES, RNA-seq) were successfully performed on FFPE tissue samples. Our RNA-seq data analysis reveals that previously reported prognostic and predictive biomarkers exhibit differential expression profiles between exceptional responders and hyper-progressors. Differential expression and gene set enrichment analyses also show increased expression of PD-L1 and upregulation of the interferon response pathways in the exceptional responders. For the WES data, we applied corrections for potential FFPE-induced artifacts and performed somatic variant calling, incorporating annotations from population and curated cancer databases, including SG10K, gnomAD, 1000 Genomes Project, ClinVar, dbSNP, and COSMIC, to aid in variant interpretation. Genomic features linked to ICI treatment response, for example tumor mutation burden, were also analyzed. Taken together, integration of the multimodal data from this unique cohort enables the identification and discovery of ICI-related biomarkers that are more relevant to the Asian population. This demonstrates that the STCC Integrated Research Data Hub can securely centralize multi-institutional cancer data and create translational value that benefits cancer patients in Singapore.