February 10, 2022
A Need for New Biomarkers
The emerging field of cancer immunotherapy has been bolstered by the development of robust biomarkers for immunotherapy response. Two of the best examples are PD-L1, a marker indicating likely success of drugs targeting PD-1, and MSI-High, a fault found in many cancers in the DNA repair pathway.
Although these two biomarkers have been critical in defining the success of early cancer immunotherapies like Opdivo and Keytruda, the highly variable nature of cancer requires constant innovation and research in this space.
Tumor Mutational Burden and Keytruda Response
Researchers at Merck did a retrospective study on their blockbuster immune checkpoint drug Keytruda, which is already approved with PD-L1 and MSI-High biomarkers, for additional indicators of successful treatment.
What their team found was that tumor mutational burden (TMB) is also a strong predictor of improved response rate in cancers treated with Keytruda. They defined a high TMB as more than 175 mutations per exome of pre-treatment tumor samples.
Out of the 1772 patients in the analysis, the objective response rate (ORR, a marker of treatment success) was 31.4% in patients with a high TMB compared to 9.5% in patients with a low TMB.
TMB: A New Cancer Biomarker
Interestingly, TMB predicts treatment response independently of the classical biomarker for Keytruda, PD-L1. This suggests that TMB may be a meaningful biomarker for cancer immunotherapies other than Keytruda in a wide range of tumor types. This brings another much-needed “general” cancer immunotherapy biomarker like MSI-High into the mix that can now be tested in different cancer types with different drugs, both retrospectively and in new studies.
Bioinformatics for Better Patient Outcomes
The in-depth, integrative analyses required to do retrospective studies of large patient cohorts like these rely on high-quality bioinformatic pipelines. Bioinformatics has been, and will continue to be, a key tool in mining biological data for new biomarkers and their efficacy. The need for new biomarkers extends far beyond cancer, and bioinformatics will advance the dream of precision medicine and the discovery of biomarkers in this field.
Jane Cook, Journalist & Content Writer, Bridge Informatics
Jane is a Content Writer at Bridge Informatics, a professional services firm that helps biotech customers implement advanced techniques in management and analysis of genomic data. Bridge Informatics focuses on data mining, machine learning, and various bioinformatic techniques to discover biomarkers and companion diagnostics. If you’re interested in reaching out, please email daniel.dacey@old.bridgeinformatics.com or dan.ryder@old.bridgeinformatics.com.
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