Tumor mutational burden as a marker for radiologic response to immune checkpoint inhibitors.

Purpose: This study aimed to evaluate the utility of tumor mutational burden (TMB) as a marker for radiologic response to immune checkpoint inhibitor (ICI) therapy at a single tertiary cancer center.

Materials and methods: In this retrospective study, out of 1044 patients treated with ICIs between January 2010 and November 2018, 75 patients (38 males and 37 females) with a mean age of 62 (range 22-87) years, who had information about TMB and adequate imaging, were included. Imaging response was determined according to iRECIST criteria. Predictors of objective response were analysed using non-parametric tests, and progression-free survival and overall survival were analysed using log-rank test.

Results: Median TMB was 7.2 mutations/mb [interquartile range: 4-13.5]. The objective radiologic response rate according to iRECIST was 26.7 % (20 patients) and the median time to best response was 61 days [IQR: 47-88 days]. Median TMB in responders (12.5 [IQR: 5-18] muts/mb) was significantly higher than in non-responders (6 [IQR: 3-12] muts/mb) (p = 0.0293). Median TMB was higher in responders in the subgroup of patients treated with Nivolumab (20 vs 4 muts/mb, P = .0043), but not significantly in those treated with Pembrolizumab (9 vs 6 muts/mb, P = .211). There was no difference in PFS (p = 0.37, Log-Rank) or OS (p = 0.053, Log-Rank) between TMB low and high groups.

Conclusion: Higher TMB was associated with objective response to ICI, however, TMB was an imperfect biomarker for PFS and OS in our study.