Journal
GENES CHROMOSOMES & CANCER
Volume 58, Issue 8, Pages 578-588Publisher
WILEY
DOI: 10.1002/gcc.22733
Keywords
biomarkers; immune checkpoint inhibitors; neoantigens; next-generation sequencing; tumor mutational burden; load
Categories
Funding
- F. Hoffman-La Roche AG
- Merck Sharp Dohme Ltd
- Memorial Sloan Kettering Cancer Center
- Johns Hopkins University
- Columbia University
- Thermo Fisher Scientific Inc
- SeraCare Life Sciences Inc
- Regeneron Pharmaceuticals Inc
- QIAGEN NV
- Pfizer Inc
- Personal Genome Diagnostics (PGDx) Inc
- OmniSeq LLC
- NeoGenomics Laboratories Inc
- Merck Company Inc
- Illumina Inc
- Guardant Health Inc
- Genentech Inc
- Foundation Medicine Inc
- EMD Serono Inc
- Caris Life Sciences Inc
- AstraZeneca LP
- ACT Genomics Company Ltd
- Bristol-Myers Squibb Company Inc
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Characterization of tumors utilizing next-generation sequencing methods, including assessment of the number of somatic mutations (tumor mutational burden [TMB]), is currently at the forefront of the field of personalized medicine. Recent clinical studies have associated high TMB with improved patient response rates and survival benefit from immune checkpoint inhibitors; hence, TMB is emerging as a biomarker of response for these immunotherapy agents. However, variability in current methods for TMB estimation and reporting is evident, demonstrating a need for standardization and harmonization of TMB assessment methodology across assays and centers. Two uniquely placed organizations, Friends of Cancer Research (Friends) and the Quality Assurance Initiative Pathology (QuIP), have collaborated to coordinate efforts for international multistakeholder initiatives to address this need. Friends and QuIP, who have partnered with several academic centers, pharmaceutical organizations, and diagnostic companies, have adopted complementary, multidisciplinary approaches toward the goal of proposing evidence-based recommendations for achieving consistent TMB estimation and reporting in clinical samples across assays and centers. Many factors influence TMB assessment, including preanalytical factors, choice of assay, and methods of reporting. Preliminary analyses highlight the importance of targeted gene panel size and composition, and bioinformatic parameters for reliable TMB estimation. Herein, Friends and QuIP propose recommendations toward consistent TMB estimation and reporting methods in clinical samples across assays and centers. These recommendations should be followed to minimize variability in TMB estimation and reporting, which will ensure reliable and reproducible identification of patients who are likely to benefit from immune checkpoint inhibitors.
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