{"entity":{"id":"tmb-high","kind":"biomarker","name":"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"],"tldr":"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.","summary":"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.","asOf":"2026-09-23","links":[{"label":"KEYTRUDA prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287"}],"tags":["biomarker","genome-wide"],"related":["msi-high","dmmr-ihc"],"cancers":["metastatic-cancer","nsclc","melanoma","urothelial"],"sections":[],"technologies":[],"targets":[],"drugs":["pembrolizumab","foundationone-cdx"],"companies":[],"institutions":[],"pathways":[],"terms":["tmb","ngs","tumour-agnostic","neoantigen"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"measurement":"tmb-threshold","scoringRule":{"text":"Somatic mutations per megabase of coding sequence counted on a validated panel; 10 or more is TMB-high for the pembrolizumab indication.","quote":"tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-authorized test","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287","sourceLabel":"KEYTRUDA prescribing information"},"thresholds":[{"value":"TMB >= 10 mutations per megabase","drugId":"pembrolizumab","cancerId":"metastatic-cancer","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9333c79b-d487-4538-a9f0-71b91a02b287","quote":"for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-authorized test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.","status":"current"}],"tests":["foundationone-cdx","foundationone-liquid-cdx","caris-mi-cancer-seek","tempus-xt","trusight-oncology-500","stratangs","omniseq-insight","altera","oncoextra","bostongene-tumor-portrait","tempus-xe"],"assays":["tmb-panel","foundationone-cdx-panel"],"companionDiagnostics":[{"device":"FoundationOne CDx","maker":"Foundation Medicine","companyId":"foundation-medicine","drugs":["pembrolizumab"],"indication":"Solid Tumors - Tissue","pma":"P170019/S016 (06/16/2020)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"}],"forPatient":"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."},"route":"/biomarkers/tmb-high/","neighbours":{"biomarker":[{"id":"ctdna-mrd-positive","kind":"biomarker","name":"ctDNA MRD positivity (molecular residual disease after curative treatment)","route":"/biomarkers/ctdna-mrd-positive/"},{"id":"dmmr-ihc","kind":"biomarker","name":"dMMR (mismatch repair deficiency by IHC)","route":"/biomarkers/dmmr-ihc/"},{"id":"msi-high","kind":"biomarker","name":"MSI-high (microsatellite instability by PCR or sequencing)","route":"/biomarkers/msi-high/"}],"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"metastatic-cancer","kind":"cancer","name":"Metastatic cancer (cancer that has spread)","route":"/cancers/metastatic-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"drug":[{"id":"foundationone-cdx","kind":"drug","name":"FoundationOne CDx / Liquid CDx","route":"/drugs/foundationone-cdx/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"term":[{"id":"neoantigen","kind":"term","name":"Neoantigen","route":"/terms/neoantigen/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"},{"id":"tumour-agnostic","kind":"term","name":"Tumour-agnostic (tissue-agnostic) approval","route":"/terms/tumour-agnostic/"}]}}