Clin Cancer Res: Quantified tumor mutation load based on ctDNA is a good predictor of whether metastasis NSCLC patients will benefit from immunotherapy

Tumor mutation load (TMB) has been shown to predict the survival benefits of patients with non-small cell lung cancer (NSCLC) treated with immunosuper inhibitors.
the use of circulating free tumor DNA (ctDNA) to detect TMB (bTMB) in the blood has a real advantage over TMB (tTMB) in the test tissue;
the analysis, verification and clinical application of a new bTMB algorithm are reported in this paper.
clinically validated data set was derived from the Phase III MYSTIC trial, which evaluated the use of durvalumab (anti-PD-L1 antibody) ± tremelimumab (anti-cytotoxic T lymphocyte-related antigen 4 antibodies) or chemotherapy as a first-line therapy to treat metastatic NSCLC.
also evaluated the patients' bTMB (GuardantOMNI) and tTMB (FoundationOne CDx experiments).
study process and the patient's bTMB score were detected in the ctDNA taken from plasma samples in most patients, followed by bTMB calculations.
effective TMB score success rate for bTMB groups is higher than for tTMB groups (81% vs 63%).
latest P-values from this validation analysis confirm that bTMB≥20 mutations/mega-bases (mut/Mb) can be selected as the most appropriate threshold to benefit from the durvalumab-tremelimumab combined treatment.
of mutation-rich paths in patients with high TMB (bTMB≥20 mut/Mb or tTMB ≥10 mut/Mb), this study demonstrates the feasibility, accuracy, and repeatability of quantifying plasma bTMB with the GuardantOMNI CTDNA platform.
with the new bTMB algorithm and the best bTMB threshold (≥20 mut/Mb), high bTMB is a predictive indicator that metastasis NSCLC patients benefit from durvalumab-tremelimumab or chemotherapy.