The association between tumor mutational burden and prognosis is dependent on treatment context

Abstract
In multiple cancer types, high tumor mutational burden (TMB) is associated with longer survival after treatment with immune checkpoint inhibitors (ICIs). The association of TMB with survival outside of the immunotherapy context is poorly understood. We analyzed 10,233 patients (80% non-ICI-treated, 20% ICI-treated) with 17 cancer types before/without ICI treatment or after ICI treatment. In non-ICI-treated patients, higher TMB (higher percentile within cancer type) was not associated with better prognosis; in fact, in many cancer types, higher TMB was associated with poorer survival, in contrast to ICI-treated patients in whom higher TMB was associated with longer survival.
Funding Information
  • U.S. Department of Health & Human Services | National Institutes of Health (R01 DE027738)
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute (P30 CA008748)
  • The Jayme and Peter Flowers Fund, the Sebastian Nativo Fund, the Catherine and Frederick Adler Junior Faculty Chair, and Cycle for Survival.
  • Fundación Alfonso Martín Escudero
  • U.S. Department of Health & Human Services | National Institutes of Health (R01 CA205426, R35 CA232097)
  • Pershing Square Sohn Cancer Research Foundation, the PaineWebber Chair, Stand Up To Cancer, and the STARR Cancer Consortium,