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TMB counts how many mutations a tumour carries per million DNA letters. Ten or more, measured by FoundationOne CDx, allows pembrolizumab for almost any solid tumour after other treatment has failed.
Tumour mutational burden is the number of somatic non-synonymous (and, on some panels, synonymous) mutations per megabase of sequenced coding DNA, estimated from a large targeted panel and calibrated to whole-exome values. Pembrolizumab's US label (June 2020, KEYNOTE-158) covers unresectable or metastatic TMB-H solid tumours defined as >= 10 mutations per megabase by an FDA-authorised test, after prior treatment and with no satisfactory alternative; FoundationOne CDx is the listed companion diagnostic. Because panels differ in gene content and algorithms, a TMB of 10 on one assay is not the same as 10 on another; the label's limitation of use notes the benefit was not established in patients with central nervous system cancers. TMB is a genome-wide readout with no parent gene, so it sits under no target here.
If a FoundationOne CDx report gives a TMB of 10 or more mutations per megabase, pembrolizumab is on label for your cancer once other treatments have been tried, whatever the organ it started in. A TMB from a different test may use a different scale; ask whether the number was measured on an FDA-authorised assay before treating it as the same threshold.
Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.
Somatic mutations per megabase of coding sequence counted on a validated panel; 10 or more is TMB-high for the pembrolizumab indication.
“tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-authorized test”
KEYTRUDA prescribing information| Threshold | Drug | Cancer | Regulator | Source |
|---|---|---|---|---|
| TMB >= 10 mutations per megabase | Pembrolizumab | Metastatic cancer (cancer that has spread) | FDA | label |
| Device | Maker | Indication and sample | Drug | PMA / 510(k) |
|---|---|---|---|---|
| FoundationOne CDx | Foundation Medicine | Solid Tumors - Tissue | Pembrolizumab | P170019/S016 (06/16/2020) |
Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.
HER2 is as frequent in India as in the West, so HER2 testing pays off in the highest-incidence population, while tumour-agnostic immunotherapy markers will rarely apply. The paper also shows plasma testing is feasible where tissue is scarce.
It is the positive half of the tumour mutational burden story and it applies only to single-agent immunotherapy, which is the setting fewest patients are treated in.
This is the result that ended tumour mutational burden as a practical selector in lung cancer: in the regimen most patients receive, it selects nobody, and neither do the co-mutations most often quoted as reasons to withhold immunotherapy.
It is the strongest case that mutation burden is real biology in lung cancer and, at the same time, the clearest demonstration that its threshold is not fixed, which is why it never became a reliable selector.
This is the fusion and immune-marker table for the wild-type minority, the group in which RNA sequencing pays for itself.
The reference Western cohort for gallbladder cancer frequencies, deposited on cBioPortal as gbc_mskcc_2022, where the per-gene sample counts on OnCo were read. It supports panel testing at diagnosis: one patient in three has a targetable finding.
The exome-level TMB here (0.82 per megabase) is an order of magnitude below panel estimates, a warning against comparing TMB across assays; and the survival signal sits in the microenvironment, which is where immunotherapy biomarkers for this disease may have to be found.
For the minority of patients whose tumours express a lot of PD-L1, a single antibody outperforms chemotherapy and is far easier to take. The word minority is the point: the same drug in the same disease at lower PD-L1 gives much less.
Shares Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab, Prevalence and mutational determinants of high tumor mutation burden in breast cancer, Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden, Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer.
Shares Triple-negative breast cancer (TNBC), Pancreatic ductal adenocarcinoma, Prostate cancer and the tags biomarker, genome-wide.
Shares Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention, Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma, FoundationOne CDx / Liquid CDx, Tumour-agnostic (tissue-agnostic) approval and the tag biomarker.
Shares Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention, Tumour-agnostic (tissue-agnostic) approval, Next-generation sequencing (NGS), Gallbladder cancer and the tag biomarker.
Shares Association of high tumor mutation burden in non-small cell lung cancers with increased immune infiltration and improved clinical outcomes of PD-L1 blockade across PD-L1 expression levels, Associations of tissue tumour mutational burden and mutational status with clinical outcomes in KEYNOTE-042, Molecular determinants of response to anti-PD-1 and anti-PD-L1 blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing, Gallbladder cancer and the tag biomarker.
Shares CheckMate 026: first-line nivolumab in stage IV or recurrent non-small-cell lung cancer, Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden, Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC, Non-small-cell lung cancer and the tag biomarker.
Shares Tumor mutational burden and PTEN alterations as molecular correlates of response to PD-1/L1 blockade in metastatic triple-negative breast cancer, FoundationOne CDx / Liquid CDx, Metastatic triple-negative breast cancer, Triple-negative breast cancer (TNBC) and the tag biomarker.
Shares FoundationOne CDx / Liquid CDx, Tumour-agnostic (tissue-agnostic) approval, Metastatic cancer (cancer that has spread), Colorectal cancer and the tag biomarker.