Tumor mutational burden assessment in non-small-cell lung cancer samples: results from the TMB2 harmonization project comparing three NGS panels

• DOI: 10.1136/jitc-2020-001904
• Publication Date: 2021-05-07T15:30:42Z
• Authors: Javier Ramos-Paradas; Susana Hernández-...; David Lora; Elena Sanchez; Aranzazu Rosado; Tamara Caniego-Casas; Nuria Carrizo; Ana Belén Enguita; María Teresa Muño...; Borja Rodriguez; Urbicio Perez-Gon...; David Gómez-Sánchez; Irene Ferrer; Santiago Ponce Aix; Ángel Nuñez Buiza; Pilar Garrido; José Palacios; Fernando Lopez-Rios; Eva M Garrido-Martin; Luis Paz-Ares
• Keywords: Concordance; Concordance correlation coefficient

Tumor mutational burden (TMB) is a recently proposed predictive biomarker for immunotherapy in solid tumors, including non-small cell lung cancer (NSCLC). Available assays TMB determination differ horizontal coverage, gene content and algorithms, leading to discrepancies results, impacting patient selection. A harmonization study of assessment with available cohort patients NSCLC urgently needed.We evaluated the obtained two marketed next generation sequencing panels: TruSight Oncology 500 (TSO500) Oncomine Mutation Load (OTML) versus reference assay (Foundation One, FO) 96 samples. Additionally, we studied level agreement among three methods respect PD-L1 expression checked different immune infiltrates TMB, performed an inter-laboratory reproducibility study. Finally, adjusted cut-off values were determined.Both panels showed strong FO, concordance correlation coefficients (CCC) 0.933 (95% CI 0.908 0.959) TSO500 0.881 0.840 0.922) OTML. The corresponding CCCs 0.951 (TSO500-FO) 0.919 (OTML-FO) tumors <1% cells expressing (PD-L1<1%; N=55), 0.861 0.722 PD-L1≥1% (N=41). Inter-laboratory analyses higher TSO500. No significant differences found terms infiltration TMB. Adjusted 10 muts/Mb FO needed be lowered 7.847 8.380 ensure sensitivity >88%. With these cut-offs, positive value was 78.57% 67.82 89.32) negative 87.50% 77.25 97.75) TSO500, while OTML they 73.33% 62.14 84.52) 86.11% 74.81 97.41), respectively.Both exhibited robust analytical performances assessment, stronger concordances expression. reproducibility. cut-offs each optimal overlap FO.