Microsatellite-Stable Tumors with High Mutational Burden Benefit from Immunotherapy

The relationship between MSI status and TMB across diverse malignancies. A, Distribution of MSI status and mutational burden among various tumor histologies (N = 148,803). B, Of 148,803 total patients (with 2,179 being MSI-high and 9,762 being TMB-high), (i) 389 patients are MSI-high and TMB-low or TMB-intermediate, (ii) 1,790 patients are MSI-high and TMB-high, and (iii) 7,972 patients are MS-stable and TMB-high. C, Median PFS for MS-stable tumors dichotomized by TMB. The median PFS for TMB-high tumors compared with TMB-low to -intermediate tumors was 26.8 months versus 4.3 months [P = 0.0173; HR 0.42 (95% confidence interval, 0.22–0.77)]. D, Median OS for MS-stable tumors dichotomized by TMB. The median OS for TMB-high tumors compared with TMB-low to -intermediate tumors was not reached versus 16.3 months [median follow-up of 17.2 months; P = 0.0635; HR 0.4581 (95% confidence interval, 0.20–1.0)]. PFS and OS were calculated by the method of Kaplan and Meier (P values by log-rank test).