323PNovel tumour mutation score versus tumour mutation burden in predicting survival after immunotherapy in pan-cancer from MSK-IMPACT cohort

Background Tumor mutation burden (TMB) may predict immune checkpoint inhibitor (ICI) response. TMB calculation included all nonsynonymous somatic mutations, but not all mutations were favorable and the efficient of TMB is attenuated by including adverse mutations. Moreover, no universal cutoff value of high TMB hindered its application in practice. Methods Tumor mutation score (TMS), defined as number of genes with nonsynonymous somatic mutations, was compared with TMB in 10,336 cancer patients from MSK-IMPACT cohort. TMS55, TMS of 55 favorable prognosis genes and TMB were calculated and compared in 1,661 advanced cancer patients treated with ICI and 3,840 matching non-ICI patients of ten major cancer types. Results TMS55 was significantly associated with TMB. In 1,661 ICI patients, high TMS55 (TMS55>5) was more robust than high TMB (highest 20% in each histology) in predicting better overall survival. Separately, TMS55 was significantly associated with improved survival in more tumor types than TMB with smaller hazard ratio values, especially in non-small cell lung cancer, melanoma, bladder cancer and colorectal cancer. Conversely, high TMS55 and TMB predicted worse overall survival in 3,840 non-ICI patients. Conclusions Novel TMS55 might be better than TMB as biomarker for patients treated with ICI and customized TMS might substitute non-selective TMB as mutation-based biomarker. Easy calculation and universal cutoff value of TMS will not be affected across platforms and is more feasible in clinical, which may greatly promote its application in clinical with further validations. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.