biomarkersBiomarker

TMB-high (tumour mutational burden >= 10 mutations per megabase)

aka TMB-H, TMB-high, TMB high, tumor mutational burden, tumour mutational burden, TMB >= 10 mut/Mb, TMB ≥10, TMB-H solid tumors, bTMB, blood TMB

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.

Genome-wide readoutOther genome-wide readouts1p/19q codeletion ctDNA MRD positivity All readouts

TMB 1 approval thresholdgenome-wide

What it means for a patient

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.

Scoring rule

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

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
TMB >= 10 mutations per megabase	Pembrolizumab	Metastatic cancer (cancer that has spread)	FDA	label

Drugs whose label names it

Pembrolizumab

Companion diagnostics (FDA list)

Device	Maker	Indication and sample	Drug	PMA / 510(k)
FoundationOne CDx	Foundation Medicine	Solid Tumors - Tissue	Pembrolizumab	P170019/S016 (06/16/2020)

Tests that measure it

FoundationOne CDx Tumour mutational burden (FoundationOne CDx and equivalents)BostonGene Tumor Portrait Tempus xT and xT CDx Tempus xE FoundationOne CDx FoundationOne Liquid CDx Caris MI Cancer Seek StrataNGS Illumina TruSight Oncology 500 Natera Altera Exact Sciences OncoExTra Labcorp OmniSeq INSIGHT

Trials that name this readout

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.