Nature reviews | CliniCal OnCOlOgy tumour mutational burden (tMB) is a promising biomarker of a response to immunecheckpoint inhibitors, independent of programmed cell death 1 ligand 1 (PDL1) status. tMB… Click to show full abstract
Nature reviews | CliniCal OnCOlOgy tumour mutational burden (tMB) is a promising biomarker of a response to immunecheckpoint inhibitors, independent of programmed cell death 1 ligand 1 (PDL1) status. tMB is usually measured in DNa from tumour tissue samples through wholeexome sequencing (wes) or sequencing of cancer gene panels (CGPs). New data support the use of plasma cellfree DNa to determine the blood tMB (btMB) as a less invasive and more convenient alternative. a novel CGP for tMB assessment was developed and validated virtually using The Cancer Genome Atlas WES data from 9,205 specimens of 33 different cancer types. this CGP panel, NCCGP150, encompasses the entire exonic regions of 150 rationally selected genes and had a correlation with the wes data similar to that of established CGPs (such as MsKiMPaCt and F1CDx). when NCCGP150 was applied to a published data set comprising 34 patients with nonsmall-cell lung cancer (NsCLC) treated with antiprogrammed cell death 1 (PD-1) antibodies, a greater than median tMB was associated with better progressionfree survival (PFs; Hr 0.36, 95% Ci 0.14–0.93; P = 0.03). assessment of matched tumour tissue and plasma samples from 48 patients with advancedstage NsCLC using wes and NCCGP150, respectively, resulted in a spearman correlation coefficient between tissue tMB and btMB of 0.62. at the median tissue tMB (75), the optimal btMB threshold was ≥ 6, with a sensitivity and specificity of 0.88 and 0.71, respectively. in an independent cohort of 50 patients with advancedstage NsCLC treated with antiPD-(L)1 antibodies, those with a btMB ≥6 (n = 28) had superior objective response rates (39.3% versus 9.1%; P = 0.02) and PFs (Hr 0.39; 95% Ci 0.18–0.84; P = 0.01). these relationships held upon multivariate analysis. in keeping with previous evidence for tissue tMB, btMB and PDL1 status were not correlated. these findings warrant testing of btMB as a biomarker in prospective trials.
               
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