Resumen
Recently, patients with high-TMB tumors received agnostic FDA approval to be treated with pembrolizumab. However, some high-TMB patients do not show clinical benefits from this strategy. In this manuscript, we investigated a large cohort of 488 patients with TMB = 10 mut/Mb treated with the following immune checkpoint inhibitors (ICIs), and correlated the clinical outcomes with the distinct somatic mutational profile of tumors: monoclonal antibody directed against programmed cell death protein-1 or monoclonal antibody directed against programmed cell death ligand 1 (anti-PD-1/anti-PD-L1); monoclonal antibody directed against cytotoxic T lymphocyte-associated antigen (anti-CTLA-4); combined treatment regimen including one anti-PD-1/anti-PD-L1 and one anti-CTLA-4 (ICIs combination). We know that some genomic alterations in TMB-high patients are already documented to help define prognosis and outcomes during immunotherapy. Conversely, other variables, such as MSI status, age, or gender, were not important to predict response to ICI treatment in this scenario, which could hypothesize the presence of a response prediction hierarchy. Thus, we believe that our manuscript is of broad interest to the general oncology community and can be used to better select patients for ICI treatment.