Tumor mutational burden for the prediction of PD-(L)1 blockade efficacy in cancer: challenges and opportunities

X Wang; G Lamberti; A Di Federico; J Alessi; R Ferrara; M L Sholl; M M Awad; Vokes N; B Ricciuti

doi:10.1016/j.annonc.2024.03.007

Tumor mutational burden for the prediction of PD-(L)1 blockade efficacy in cancer: challenges and opportunities

Ann Oncol. 2024 Mar 25:S0923-7534(24)00084-X. doi: 10.1016/j.annonc.2024.03.007. Online ahead of print.

Authors

X Wang¹, G Lamberti², A Di Federico², J Alessi², R Ferrara³, M L Sholl⁴, M M Awad², Vokes N⁵, B Ricciuti⁶

Affiliations

¹ Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States.
² Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, United States.
³ University Vita-Salute San Raffaele, Milan, Italy; Department of Medical Oncology, IRCCS San Raffaele, Milan, Italy.
⁴ Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, United States.
⁵ Department of Thoracic Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA.
⁶ Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, United States. Electronic address: biagio_ricciuti@dfci.harvard.edu.

PMID: 38537779
DOI: 10.1016/j.annonc.2024.03.007

Abstract

Tumor mutational burden (TMB) is a biomarker that measures the number of somatic mutations in a tumor's genome. TMB has emerged as a predictor of response to immune checkpoint inhibitors (ICIs) in various cancer types, and several studies have shown that patients with high TMB have better outcomes when treated with PD-(L)1-based therapies. Recently, the FDA has approved TMB as a companion diagnostic for the use of pembrolizumab in solid tumors. However, despite its potential, the use of TMB as a biomarker for immunotherapy efficacy is limited by several factors. Here we review the limitations of TMB in predicting immunotherapy outcomes in patients with cancer and discuss potential strategies to optimize its use in the clinic.

Publication types

Review