Immuno-oncology is an ever growing field that has seen important progress across the spectrum of
cancers. Responses can be deep and durable. However, as only a minority of patients respond to checkpoint inhibition, predictive
biomarkers are needed.
Cancer is a
genetic disease arising from the accumulation of somatic mutations in the
DNA of affected cells.
Tumor mutational burden (TMB), represents the number of somatic mutations in a
tumor that form neoantigens, responsible for the immunogenicity of
tumors. Randomized controlled trials have so far failed to show a survival benefit when stratifying patients by tissue TMB. TMB has also been evaluated in plasma (PTMB). PTMB is anticipated to represent the biology of the entire
cancer, whereas obtaining tissue of an amenable primary or a metastatic lesion may be prone to sampling bias because of
tumor heterogeneity. For this reason, we are evaluating the correlation between TMB and PTMB, and prospectively evaluating the impact of these
biomarkers on clinical outcomes. We also discuss the technical difficulties inherent to performing and comparing these analyses. Furthermore, we evaluate the correlation between the evolution of PTMB during an
immunotherapy treatment and response at 3 and 6 months, as we believe PTMB may be a dynamic
biomarker. In this paper, we present results from the first 4 patients in this project.