# A single calibrated tumour mutational burden across all sequencing panels

Source: https://onco.cc/ideas/idea-tr2-tmb-calibration-standard/  
OnCo record `idea-tr2-tmb-calibration-standard` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- Friends of Cancer Research TMB Harmonization: https://friendsofcancerresearch.org/tmb/

## Connected records

- companies: [Foundation Medicine (Roche)](https://onco.cc/companies/foundation-medicine/), [Tempus AI](https://onco.cc/companies/tempus/)
- technologies: [Whole-exome & whole-genome sequencing](https://onco.cc/technologies/wes-wgs/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- terms: [Next-generation sequencing (NGS)](https://onco.cc/terms/ngs/), [Tumour mutational burden (TMB)](https://onco.cc/terms/tmb/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/)
- key papers: [KEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation](https://onco.cc/key-papers/paper-keynote-189-nejm-2018/), [KEYNOTE-564: a year of pembrolizumab after kidney cancer surgery](https://onco.cc/key-papers/paper-keynote-564-nejm-2021/)

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