Inappropriate Use of the Same Cutoff by Different Sequencing Panels for Tumor Mutation Burden as Immunotherapy Biomarker

To the Editor We read with great interest the article by Valero et al¹ that described response rates, with respect to tumors with 10 or more mutations per megabase, in a cohort of 1678 patients treated with immune checkpoint inhibitors (ICIs). Including this study, the same research group reported 3 related studies recently. The other 2 studies, by Samstein et al² and Valero et al,³ reported the predictive value of tumor mutation burden (TMB) on immunotherapy with the top 20 percentile (20%) as the cutoff and the association of TMB with survival with or without the immunotherapy context in patients with cancer, respectively. Although most of the patients with cancer receiving immunotherapy in these studies overlapped and some of the results were also duplicated, these 3 studies reported real-world data on immunotherapy, provided important clues for the clinical application of TMB as a biomarker, and guided possible ICI trial design. For this research, we have 2 comments.