Tumor Mutational Burden (TMB)

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This type of biomarker is currently under study to evaluate whether it may help predict the likelihood a patient with cancer will benefit from immuno-oncology (IO) therapies.

Different tests may report different measurements, and since there is currently no one way of calculating TMB it is difficult to use as a biomarker. To achieve consistency and accurate reporting across tests, it is imperative to create some sort of standardization to arrive at clinically-meaningful results, which will support informed decision-making for patients.

Friends of Cancer Research (Friends) has convened stakeholders across all health sectors to review the current methods of TMB calculation and reporting and created a consensus solution on how best to standardize them. The group has worked on large collaborative analytical validation studies to support a standardized method of TMB measurement and an alignment approach, which will help improve patient care through consistent TMB reporting in a clinical setting despite differences in the testing assay used. Ultimately, this project will help ensure consistent identification of patients who are likely to respond to IO therapies.

TMB Harmonization Project Overview


TMB Harmonization Project Results:

  • Click HERE to view the full recap for our July 14, 2020 Virtual Symposium, The Future Use of Complex Biomarkers
  • Click HERE to view the full recap for our July 23, 2020 Virtual Meeting, TMB Results: The Future Use of Complex Biomarkers


Phase 1

  • In silico assessment of variation in TMB quantification across diagnostic platforms: Phase 1 of the Friends of Cancer Research Harmonization Project
  • Establishing guidelines to harmonize tumor mutational burden (TMB): in silico assessment of variation in TMB quantification across diagnostic platforms: phase I of the Friends of Cancer Research TMB Harmonization Project (Friends manuscript)
  • Tumor mutational burden standardization initiatives: Recommendations for consistent tumor mutational burden assessment in clinical samples to guide immunotherapy treatment decisions (Collaborative Manuscript)
  • Harmonization and Standardization of Panel-Based Tumor Mutational Burden (TMB) Measurement: Real-World Results and Recommendations of the QuIP Study (Collaborative Manuscript)
  • Spatial and Temporal Heterogeneity of Panel-Based Tumor Mutational Burden in Pulmonary Adenocarcinoma: Separating Biology From Technical Artifacts (Collaborative Manuscript)


Phase 2

  • Aligning Tumor Mutational Burden (TMB) quantification across diagnostic platforms: Phase 2 of the Friends of Cancer Research TMB Harmonization Project (Collaborative Manuscript)
  • Alignment of TMB measured on clinical samples: Phase 2B of the Friends of Cancer Research TMB Harmonization Project
  • TMB standardization by alignment to reference standards: Phase II of the Friends of Cancer Research TMB Harmonization Project


Phase 3


TMB Harmonization Working Group Members:

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


The Background:

  • The use of IO therapies has increased dramatically in recent years. Immune checkpoint inhibitors (ICIs) are drugs that harness the patient’s own immune system to fight cancer and have demonstrated a durable response and improved survival in a limited fraction of patients with cancers of the lung, head and neck, bladder, and melanoma.
  • Recent discoveries have shown an association between a higher number of mutations found in a patient’s tumor and an elevated immune response. This was also observed in patients who received ICIs. The higher the number of tumor mutations, the better the patient’s outcome.
  • Measuring the tumor’s mutation burden may be a good predictor of which patients would most likely benefit from treatment from ICIs.