LBA17Harmonization study of tumour mutational burden determination in non-small cell lung cancer (NSCLC)

• Published in: Annals of oncology Vol. 30; no. Supplement_5
• Main Authors: Garrido-Martin, E M, Ramos-Paradas, J, Hernandez Prieto, S, Sanchez, E, Rosado, A, Caniego-Casas, T, Carrizo, N, Enguita, A B, Muñoz-Jiménez, M T, Rodriguez, B, Perez-Gonzalez, U, Gomez Sanchez, D, Ferrer, I, Ponce Aix, S, Nuñez Buiza, A, Garrido, P, Palacios, J, Lopez-Rios, F, Paz-Ares, L
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01.10.2019
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdz394.002

Abstract Background Tumour mutational burden (TMB) is an emerging predictive biomarker for patients with NSCLC treated with checkpoint inhibitors. A number of gene panels are available for TMB calculation, each with different characteristics, including the number of genes and the selected individual genes, and distinct informatics algorithms that may lead to different results. We have performed a correlation study of 3 panels in a large cohort of clinically annotated NSCLC patients. Methods We have blindly evaluated the concordance of tissue TMB assessments of two different commercially available panels: TSO500 (performed at HU 12 de Octubre) and Oncomine TML (performed at CIOCC), with Foundation One® CDx (F1CDx-Penzberg, Germany). A cohort of 100 early stage NSCLC tumour samples is being utilized. PD-L1 expression was analyzed in all samples with 22C3 PharmDX. Results The determination of TMB for all panels was calculated as total number of mutations (synonym plus non-synonym) per megabase of exonic DNA. Four samples did not have enough sequencing depth for TML panel (n = 96 was used for all correlations). TMB values correlated with F1CDx with a R2 =0.8775 for TSO500; and with a R2 = 0.8119 for TML. The correlation between TSO500 and TML was R2 = 0.8545. Results obtained for each panel are indicated in the table below. Additionally, TMB values were evaluated in the samples grouped by < 1%, >1% and >50% of PD-L1 expression. In tumours PD-L1<1% (n = 55), TMB values correlated with F1CDx with a R2 = 0.9120 (TSO500) and a R2 = 0.8768 (TML), respectively. In tumours PD-L1>1% (n = 41), TMB values correlated with F1CDx with a R2 = 0.7466 (TSO500) and a R2 = 0.5735 (TML), respectively. Table:LBA17NSCLC Cohort (n = 96)TSO500TMLF1CDxTotal TMB Range (muts/Mb) Average (muts/Mb) Median (muts/Mb) % of samples with TMB >10 muts/Mb % of samples with TMB >13 muts/Mb % of samples with TMB >16 muts/Mb1-84 13 9 46% 31% 20%0-60 13 10 50% 38% 24%0-74 14 10 51% 35% 28%PDL1 <1% (n = 55)TSO500TMLF1CDxTMB high (≥10) TMB med/low (<10)53% 47%64% 36%51% 49%PDL1 >1% (n = 55)TSO500TMLF1CDxTMB high (≥10) TMB med/low (<10)59% 41%63% 37%51% 49%PDL1 >50% (n = 10)TSO500TMLF1CDxTMB high (≥10) TMB med/low (<10)70% 30%80% 20%40% 60% Conclusions There is a strong correlation between TMB determined by TSO500 and TML panels with F1CDx, particularly for tumours with low PD-L1 expression. The range of TMB values is lower with TSO500 and TML, for samples determined TMBhigh by F1CDx. Cut-off values may be lowered for these panels in order to meet F1CDx TMB categories. Legal entity responsible for the study Fundacion para la Investigacion Biomedica del Hospital Doce de Octubre, Madrid, Spain. Funding Bristol-Myers Squibb. Disclosure E.M. Garrido-Martin: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: Illumina. S. Hernandez Prieto: Honoraria (institution): Roche; Honoraria (institution): Thermo Fisher; Honoraria (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (institution): Bristol-Myers Squibb; Honoraria (institution): AbbVie. S. Ponce Aix: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Lilly; Travel / Accommodation / Expenses: AstraZeneca. P. Garrido: Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Roche; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boerhinger Ingelheim; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy: AbbVie; Advisory / Consultancy, Research grant / Funding (institution): Guardant Health; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (institution), Advisory / Consultancy: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (institution): Sysmex; Honoraria (institution), Advisory / Consultancy: Blueprint Medicines; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony: Gilead; Speaker Bureau / Expert testimony: Rovi; Honoraria (institution): Pharmamar; Honoraria (institution): Celgene; Honoraria (institution): Sanofi; Honoraria (institution): GSK, Theradex Oncology. F. Lopez-Rios: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Thermo Fisher; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: AbbVie; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy: Bayer. L. Paz-Ares: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pharmamar; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Servier; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Sysmex; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Incyte; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Adacap; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Blueprint. All other authors have declared no conflicts of interest.