Tumor mutational burden as a predictive biomarker for checkpoint inhibitor immunotherapy.

Human Vaccines & Immunotherapeutics
Mark LeeLuc G T Morris

Abstract

Immune checkpoint inhibitor (ICI) therapies can achieve meaningful tumor responses in a subset of patients with most types of cancer that have been investigated. However, the majority of patients treated with these drugs do not experience any clinical benefit. Because not all patients benefit from ICIs, and some may experience more meaningful tumor response if treated with chemotherapy or other treatments, there is a compelling need for predictive biomarkers to facilitate more informed selection of therapy. Tumor mutational burden (TMB) is one feature of a tumor that has predictive value for ICI therapy across multiple cancer types. In a pan-cancer analysis of over 1,600 patients, higher TMB was associated with longer survival and higher response rates with ICI therapy. While this effect was seen in the majority of cancer types, indicating that TMB underlies fundamental aspects of immune-mediated tumor rejection, the optimal predictive cut-point varied widely by histology, suggesting that there is unlikely to be one tissue-agnostic definition of high TMB that is useful for predicting ICI response. More comprehensive predictive models integrating TMB with other factors - including genetic, immunologic, and clinicopathologic mark...Continue Reading

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Citations

May 13, 2020·Journal for Immunotherapy of Cancer·Alberto PucciniMohamed E Salem
Aug 1, 2020·Frontiers in Immunology·Andrea BotticelliPaolo Marchetti
Jan 30, 2021·Future Oncology·Santosh GautamAnirban Basu
May 29, 2021·Journal of Comparative Effectiveness Research·Santosh GautamAnirban Basu
Jun 11, 2021·Cancer Treatment Reviews·M de Vries-BrillandL Albigès
Aug 27, 2021·Frontiers in Immunology·Andrea BotticelliPaolo Marchetti

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Methods Mentioned

BETA
targeted
exome sequencing

Software Mentioned

MSK
IMPACT

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