Checkpoint inhibitor-based immunotherapy has revolutionized treatment for cancer malignancies. Alas, immune-related adverse effects are not negligible and some patients do not respond to therapy. For these reasons, it has become evident that predictive biomarkers of response are needed for these novel agents. Recently, tumor mutational burden, as detected by tissue next-generation sequencing, has been shown to correlate with response to checkpoint inhibitors in several malignancies. In the present study, the researchers sought to investigate the association between hypermutated blood-derived circulating tumor DNA (ctDNA) and checkpoint inhibitor response to avoid tissue biopsy which is costly and invasive. The researchers assessed the association by next-generation sequencing in 69 patients with diverse malignancies over time. The study demonstrates a correlation between high alteration number detected in blood-derived circulating tumor DNA and favourable outcomes, including overall response, progression-free and overall survival with checkpoint inhibitor-based immunotherapy. This data shows liquid biopsy to be a viable, non-invasive, predictive biomarker for checkpoint inhibitor response.
Hypermutated circulating tumor DNA: correlation with response to checkpoint inhibitor-based immunotherapy
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