Analytical Validation of Blood-Derived Tumor Mutation Burden (bTMB) Assays: A Joint Consensus Recommendation of the BLOODPAC bTMB Analytical Validation Working Group

A new perspective from the BLOODPAC bTMB Analytical Validation Working Group, published in the Journal of Molecular Diagnostics, outlines key technical and biological considerations for the analytical validation of blood-based tumor mutational burden (bTMB) assays. While bTMB holds promise as a biomarker for predicting response to immunotherapy in patients with advanced and metastatic solid tumors, the complexity of the biomarker—and its detection in circulating tumor DNA—demands careful validation to avoid confounding clinical results.

This publication provides a conceptual framework to guide developers in demonstrating the analytical performance of bTMB assays, including pre-analytical variable management and strategies to distinguish tumor-specific mutations from germline or clonal hematopoiesis-associated alterations. The Working Group also emphasizes the importance of transparent data sharing through resources like the BLOODPAC Data Commons to accelerate harmonization and advancement across the field.