High Tumor Mutational Burden Correlates With Longer Survival In Immunotherapy-Naive Patients With Diverse Cancers
MOLECULAR CANCER THERAPEUTICS(2020)
摘要
Higher tumor mutational burden (TMB) has been correlated with response to checkpoint blockade immunotherapy. However, it is unclear whether TMB independently serves as a prognostic biomarker for outcomes in immunotherapy-naive patients. Here, we evaluated the relationship between TMB and overall survival in 1,415 immunotherapy-naive patients with diverse advanced malignancies. TMB was studied both as a tiered variable ( low <= 5 mutations/Mb, intermediate > 5 and < 20, high <= 20 and < 50, and very high <= 50) and as a continuous variable. Interestingly, we observed a parabolic correlation between TMB and overall survival, in which intermediate-range TMB correlated with decreased survival, whereas low and very high TMB correlated with improved outcomes (median survival: 238, 174, 195, and 350 weeks for low, intermediate, high, and very high TMB, respectively; multivariate P < 0.01). This corresponded to an HR of 1.29 (95% confidence interval, 1.07-1.54; P < 0.01) for intermediate-range TMB on multivariable survival analysis correcting for known confounders, including primary tumor of origin. These results demonstrate that TMB may have utility as a prognostic biomarker in immunotherapy-naive patients, with a protective effect at higher TMBs, and that studies of survival in immunotherapy-treated patients may need to stratify or randomize by TMB in a nonlinear fashion to account for this confounding.
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