{"entity":{"id":"idea-tr2-tmb-calibration-standard","kind":"idea","name":"A single calibrated tumour mutational burden across all sequencing panels","aka":[],"tldr":"Tumour mutational burden decides who gets immunotherapy in some settings, but every sequencing panel calculates it differently. A shared calibration would make the number mean the same thing everywhere.","summary":"The Friends of Cancer Research TMB Harmonization Project showed that panel-derived TMB values can be aligned to whole-exome TMB with panel-specific calibration and reference samples. Yet the pembrolizumab approval for TMB above 10 mutations per megabase was tied to a single assay. Requiring each panel to report a calibrated TMB traceable to a common reference set, with published calibration curves, would make the biomarker portable across assays.","asOf":"2026-09-08","links":[{"label":"Friends of Cancer Research TMB Harmonization","url":"https://friendsofcancerresearch.org/tmb/"}],"tags":[],"related":["foundation-medicine","tempus"],"cancers":[],"sections":[],"technologies":["wes-wgs"],"targets":[],"drugs":["pembrolizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["tmb","ngs"],"trials":[],"people":[],"bottlenecks":["b-biomarker-validation","b-immunotherapy-response"],"keyPapers":["paper-keynote-189-nejm-2018","paper-keynote-564-nejm-2021"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Calibrated TMB reporting will reduce the inter-assay disagreement in classifying tumours as TMB-high from around 20 to 30% to under 10%.","rationale":"The harmonisation project has already provided the method and reference cell lines; adoption, not science, is the gap.","test":"Have ten commercial panels report calibrated TMB on a shared 100-sample set; measure classification agreement before and after calibration.","maturity":"early-clinical","actor":"industry","cost":"small","horizonYears":2},"route":"/ideas/idea-tr2-tmb-calibration-standard/","neighbours":{"company":[{"id":"foundation-medicine","kind":"company","name":"Foundation Medicine (Roche)","route":"/companies/foundation-medicine/"},{"id":"tempus","kind":"company","name":"Tempus AI","route":"/companies/tempus/"}],"technology":[{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"term":[{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"},{"id":"tmb","kind":"term","name":"Tumour mutational burden (TMB)","route":"/terms/tmb/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"paper":[{"id":"paper-keynote-189-nejm-2018","kind":"paper","name":"KEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation","route":"/key-papers/paper-keynote-189-nejm-2018/"},{"id":"paper-keynote-564-nejm-2021","kind":"paper","name":"KEYNOTE-564: a year of pembrolizumab after kidney cancer surgery","route":"/key-papers/paper-keynote-564-nejm-2021/"}]}}