TMB Harmonization Project

Tumor Mutational Burden Harmonization Project

Quick Links

The Tumor Mutational Burden (TMB) Harmonization Project supports the use of assays that measure TMB for treatment decision making by examining sources of variability across assays and identifying opportunities for alignment.

Historically, cancer treatment involved chemotherapy, which attacks dividing cells throughout the body, including many cells that are not cancerous. In recent years, scientific innovation has facilitated the development of targeted therapies, which can precisely attack cancer cells that have specific signals known as biomarkers, potentially providing more effective and safer treatments for patients. It is necessary to identify which patients have the biomarker and may benefit from specific targeted therapies. To help identify which patients have a specific biomarker, diagnostic developers have created tests, also known as assays.

One biomarker of interest is Tumor Mutation Burden (TMB). Research suggests that patients with a higher number of tumor mutations are more likely to benefit from targeted treatment with immune checkpoint inhibitors (ICIs). Prior to initiation of the TMB Harmonization project, there was a lack of standardization for TMB calculation and reporting. Findings from the project highlight different tests reported different measurements, and since there is no singular way of calculating TMB it may be difficult to use as a biomarker. To achieve consistency and accurate reporting across tests, it was imperative to standardize assays to arrive at clinically meaningful results and support informed decision-making for patients. 

Friends initiated a unique collaboration with key stakeholders including pharmaceutical companies, assay developers, FDA, and academics in September 2017 to discuss the variability in how TMB is defined, analyzed, and used in clinical practice, and the need for establishing industry standards.  Throughout the course of the TMB Harmonization Project, Friends hosted discussions with project participants to develop consensus on a methodological approach to compare TMB assays, to develop a calibration tool to promote reproducibility and comparability across assays, and to provide recommendations for a clinical cutoff to support evaluation of TMB for clinical trial enrollment using a common strategy. Findings from each phase of the project were disseminated through public workshops, conferences, and manuscripts.

The results of the TMB Harmonization Project informed consensus recommendations on a standardized approach to measure TMB. If assay developers use these strategies, providers and patients will have more consistent results regardless of which assay they use to measure TMB. This project will help ensure consistent identification of patients who are likely to respond to immunotherapies and, ultimately, improve patient outcomes.

Project Outcomes

Project Partners

ACT Genomics, AstraZeneca, Biodesix, Brigham & Women’s Hospital, Bristol Myers Squibb, Caris Life Sciences, College of American Pathologists, Columbia University, the European Organisation for Research and Treatment of Cancer (EORTC), EMD Serono, Inc., the U.S. Food and Drug Administration (FDA), Foundation Medicine, Inc., Genentech, Inc., Genomic Testing Cooperative, Guardant Health, Inc., Hartwig Medical Foundation, Illumina, Inc., Intermountain Precision Genomics, Johns Hopkins University, Massachusetts General Hospital, Merck & Co., Inc., Memorial Sloan Kettering Cancer Center, MD Anderson Cancer Center, National Cancer Institute (NCI), NeoGenomics Laboratories, Inc., OmniSeq, Personal Genome Diagnostics (PGDx), Pfizer, Inc., precisionFDA, Q2 Solutions, QIAGEN, Inc., Quality in Pathology (QuIP), Quest Diagnostics, Regeneron Pharmaceuticals, Roche Diagnostics, SeraCare, Thermo Fisher Scientific, Thrive, University of Heidelberg