2020 AACR: Composite neoantigen score is more strongly associated with therapeutic response than tumor mutational burden in a cohort of late-stage anti-PD-1-treated melanoma patients
Checkpoint inhibitor therapy has demonstrated meaningful, if varied, antitumor activity, with patient response influenced by a variety of biological factors, including complex interactions between the tumor and immune system. Thus, it is of increasing interest to identify composite biomarkers integrating multiple biological features to better predict immunotherapy response. In this study we use a comprehensive tumor immunogenomics profiling platform to examine the effectiveness of our composite neoantigen score for stratifying patient response to checkpoint blockade therapy compared to tumor mutational burden and other biomarkers.
Pre-treatment tumor/normal samples from 55 unresectable, stage III/IV melanoma patients who underwent anti-PD-1 therapy were characterized to assess factors influencing response. RECIST criteria were used to evaluate tumor response to therapy, with a median follow-up of 18 months. For each patient, a single paired FFPE tumor and normal blood sample was collected and profiled using the Personalis® ImmunoID NeXT Platform®: an augmented exome/transcriptome platform and analysis pipeline, which produces comprehensive tumor mutation information, gene expression quantification, neoantigen characterization, HLA typing and allele-specific HLA loss of heterozygosity data (HLA LOH), TCR repertoire profiling and tumor microenvironment profiling. These data were then analyzed together with clinical outcome, and a composite neoantigen score computed for each patient along with other biomarkers such as tumor mutational burden (TMB).