2236P MHC-II neoantigens and copy number alterations (CNA) drive immune checkpoint inhibitor (ICI) response in metastatic melanoma (MM)

摘要: BackgroundICIs have transformed the prognosis of MM, but our understanding of mechanisms of response and resistance remains incomplete. The 100,000 Genomes Project presents a melanoma cohort with whole genome sequencing (WGS) and detailed clinical annotation.Methods97 patients received ICIs in the 1L metastatic disease setting; ipilimumab-nivolumab (60%), anti-PD-1 monotherapy (32%), and ipilimumab (8%). Response rate was 45%. Median follow-up was 30.6 months, median time to treatment failure (TTF) 9.6 months and median overall survival (OS) not reached. From WGS, neoantigen calling, CNA and tumour purity analyses were performed, predictive variables were included in logistic regression.ResultsIncorporating MHC-II neoantigen load, CNAs and tumour purity, our multivariate model predicted response with AUC 0.86 Responders were associated with a higher number of predicted …