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A Closer Look into Phase 1 of the TMB Harmonization Project

A Closer Look into Phase 1 of the TMB Harmonization Project

The overall goal of the Friends of Cancer Research (FriendsTumor Mutational Burden (TMB) Harmonization Project  was to ensure consistency across values from different TMB tests for cancer treatment. This article provides information about Phase I of the TMB Harmonization Project and how Friends worked to address the issue of TMB standardization.

On March 26, 2020, the paper “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” was published in the Journal for ImmunoTherapy of Cancer (JITC).  An earlier blog outlines Why We Decided to Harmonize TMB as the number of mutations found in a tumor can act as a helpful biomarker. As mentioned in a previous blog post about How We Approached The Harmonization of TMB , Phase 1 investigated the differences across participating TMB tests by measuring TMB in a common set of tumor samples, using a publicly available dataset from the National Cancer Institute’s The Cancer Genome Atlas (TCGA).

Cooperation between different stakeholders is necessary to improve care and safety for patients. Currently there are many ways to measure TMB; however, different tests yield different results. This can pose a risk to patients as diagnostic testing informs what treatment a patient should receive. If TMB values from different tests are not accurate and comparable, patients may not receive the correct and necessary treatment. Once the similarities and differences between TMB tests can be identified, a tool that can improve interchangeability between TMB values and establish consistency across panels can be created.

The consortium drafted a consensus set of recommendations, that the scientific community can use, on how to conduct consistency across testing. The recommendations emphasized the need for consistent reporting, specific validation studies to ensure accuracy and precision of TMB tests, and the creation of universal reference standards for TMB estimation. These recommendations will guide the development of additional TMB tests for the scientific community.

The success of the TMB Harmonization Project is due to the collaborative nature of the project. This paper represents the power of collaboration as 11 different laboratories used publicly available data from TCGA to estimate TMB and compare these values to describe the variability across tests. From a space of sharing and cooperation, the consortium identified places to improve standardization to promote the harmonization of TMB estimation.

Due to the effort of Friends, encouraging partnerships across different organizations, we are working toward reformulating how patients receive care. Improving diagnostic tools and working toward the standardization of biomarker testing enhances patient experience by delivering safe and reliable treatments. To read the full study click here


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