Tissue-Plasma TMB Comparison and Plasma TMB Monitoring in Patients With Metastatic Non-small Cell Lung Cancer Receiving Immune Checkpoint Inhibitors.

CtDNA NSCLC TMB biomarker immune check inhibitor (ICI)

Journal

Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867

Informations de publication

Date de publication:
2020
Historique:
received: 05 12 2019
accepted: 27 01 2020
entrez: 3 3 2020
pubmed: 3 3 2020
medline: 3 3 2020
Statut: epublish

Résumé

Immuno-oncology is an ever growing field that has seen important progress across the spectrum of cancers. Responses can be deep and durable. However, as only a minority of patients respond to checkpoint inhibition, predictive biomarkers are needed. Cancer is a genetic disease arising from the accumulation of somatic mutations in the DNA of affected cells. Tumor mutational burden (TMB), represents the number of somatic mutations in a tumor that form neoantigens, responsible for the immunogenicity of tumors. Randomized controlled trials have so far failed to show a survival benefit when stratifying patients by tissue TMB. TMB has also been evaluated in plasma (PTMB). PTMB is anticipated to represent the biology of the entire cancer, whereas obtaining tissue of an amenable primary or a metastatic lesion may be prone to sampling bias because of tumor heterogeneity. For this reason, we are evaluating the correlation between TMB and PTMB, and prospectively evaluating the impact of these biomarkers on clinical outcomes. We also discuss the technical difficulties inherent to performing and comparing these analyses. Furthermore, we evaluate the correlation between the evolution of PTMB during an immunotherapy treatment and response at 3 and 6 months, as we believe PTMB may be a dynamic biomarker. In this paper, we present results from the first 4 patients in this project.

Identifiants

pubmed: 32117779
doi: 10.3389/fonc.2020.00142
pmc: PMC7028749
doi:

Types de publication

Journal Article

Langues

eng

Pagination

142

Informations de copyright

Copyright © 2020 Friedlaender, Nouspikel, Christinat, Ho, McKee and Addeo.

Références

Front Oncol. 2019 Apr 16;9:264
pubmed: 31058078
Curr Oncol. 2018 Jun;25(Suppl 1):S94-S102
pubmed: 29910652
Nat Med. 2017 Jun;23(6):703-713
pubmed: 28481359
J Immunother Cancer. 2019 Apr 3;7(1):98
pubmed: 30944026
Mayo Clin Proc. 2018 Aug;93(8):1122-1130
pubmed: 30078412
N Engl J Med. 2018 May 31;378(22):2093-2104
pubmed: 29658845
Bioinformatics. 2017 Jan 1;33(1):26-34
pubmed: 27531099
N Engl J Med. 2019 Nov 21;381(21):2020-2031
pubmed: 31562796
Gut. 2016 Apr;65(4):625-34
pubmed: 25654990
Ann Oncol. 2014 Sep;25(9):1729-35
pubmed: 25009010
Oncotarget. 2016 Nov 29;7(48):79485-79493
pubmed: 27825131
Lancet. 2019 May 4;393(10183):1819-1830
pubmed: 30955977
Nat Genet. 2019 Feb;51(2):202-206
pubmed: 30643254
Lung Cancer Manag. 2019 Nov 14;8(3):LMT17
pubmed: 31807145
PLoS One. 2017 Nov 21;12(11):e0188174
pubmed: 29161279
Clin Chem. 2002 Mar;48(3):421-7
pubmed: 11861434
Science. 2015 Apr 3;348(6230):124-8
pubmed: 25765070
Ann Oncol. 2019 Jul 1;30(7):1096-1103
pubmed: 31038663
Adv Clin Chem. 2019;89:131-188
pubmed: 30797468
Nat Biotechnol. 2013 Mar;31(3):213-9
pubmed: 23396013
Proc Natl Acad Sci U S A. 2015 Oct 6;112(40):E5503-12
pubmed: 26392541
J Clin Oncol. 2019 Mar 1;37(7):537-546
pubmed: 30620668
Eur J Cancer. 2016 Jul;62:132-7
pubmed: 27189322
Nat Med. 2018 Sep;24(9):1441-1448
pubmed: 30082870
Crit Rev Oncol Hematol. 2017 Dec;120:13-21
pubmed: 29198327
Comput Struct Biotechnol J. 2018 Feb 06;16:15-24
pubmed: 29552334
Transl Psychiatry. 2018 Oct 29;8(1):236
pubmed: 30374018
Nucleic Acids Res. 2012 Dec;40(22):11189-201
pubmed: 23066108
Nat Methods. 2018 Aug;15(8):591-594
pubmed: 30013048
Nucleic Acids Res. 2011 Oct;39(19):e132
pubmed: 21813454
JAMA Oncol. 2019 Jul 1;5(7):934-935
pubmed: 31145420
Transl Lung Cancer Res. 2018 Dec;7(6):668-677
pubmed: 30505711
J Exp Clin Cancer Res. 2011 May 06;30:50
pubmed: 21548925
Nat Mater. 2017 Nov;16(11):1155-1161
pubmed: 29035356

Auteurs

Alex Friedlaender (A)

Department of Oncology, University Hospital of Geneva (HUG), Geneva, Switzerland.

Thierry Nouspikel (T)

Service of Medical Genetics, Diagnostics Department, University Hospital of Geneva, Geneva, Switzerland.

Yann Christinat (Y)

Department of Pathology, University Hospital of Geneva, Geneva, Switzerland.

Liza Ho (L)

Department of Pathology, University Hospital of Geneva, Geneva, Switzerland.

Thomas McKee (T)

Department of Pathology, University Hospital of Geneva, Geneva, Switzerland.

Alfredo Addeo (A)

Department of Oncology, University Hospital of Geneva (HUG), Geneva, Switzerland.

Classifications MeSH