Applicability of Routine Targeted Next-generation Sequencing to Estimate Tumor Mutational Burden (TMB) in Patients Treated With Immune Checkpoint Inhibitor Therapy.
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ genetics
Female
High-Throughput Nucleotide Sequencing
/ methods
Humans
Immune Checkpoint Inhibitors
/ therapeutic use
Immunotherapy
/ methods
Lung Neoplasms
/ drug therapy
Male
Melanoma
/ drug therapy
Middle Aged
Mutation
/ genetics
Pilot Projects
Prognosis
T-Lymphocytes
/ drug effects
Tumor Burden
/ genetics
Journal
Journal of immunotherapy (Hagerstown, Md. : 1997)
ISSN: 1537-4513
Titre abrégé: J Immunother
Pays: United States
ID NLM: 9706083
Informations de publication
Date de publication:
Historique:
pubmed:
1
10
2019
medline:
2
6
2021
entrez:
1
10
2019
Statut:
ppublish
Résumé
It remains unclear whether targeted next-generation sequencing (tNGS) conveys a reliable estimate of tumor mutational burden (TMB). We sequenced 79 archival samples of immune checkpoint inhibitors (ICPIs) recipients (57% lung cancer, 43% melanoma) using Ion Ampliseq Cancer Hotspot Panel. Employing multiple cutoff values, we verified that TMB by tNGS did not correlate with response or survival following ICPI. We found enrichment of ATM mutations in ICPI-refractory tumors (P=0.01) to correlate with worse survival (4.2 vs. 10 mo, P=0.03). Limited-coverage tNGS delivers an imprecise estimate of patients' TMB but may aid identification of candidate somatic variants of predictive/prognostic significance.
Identifiants
pubmed: 31567705
doi: 10.1097/CJI.0000000000000295
pii: 00002371-202002000-00003
doi:
Substances chimiques
Biomarkers, Tumor
0
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
53-56Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Références
Goodman AM, Kato S, Bazhenova L, et al. Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther. 2017;16:2598–2608.
Buchhalter I, Rempel E, Endris V, et al. Size matters: dissecting key parameters for panel-based tumor mutational burden (TMB) analysis. Int J Cancer. 2019;144:848–858.
Pinato DJ, Howlett S, Ottaviani D, et al. Association of prior antibiotic treatment with survival and response to immune checkpoint inhibitor therapy in patients with cancer. JAMA Oncol. 2019. [Epub ahead of print].
Tsongalis GJ, Peterson JD, de Abreu FB, et al. Routine use of the Ion Torrent AmpliSeq Cancer Hotspot Panel for identification of clinically actionable somatic mutations. Clin Chem Lab Med. 2014;52:707–714.
Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348:124–128.
Ricciuti B, Kravets S, Dahlberg SE, et al. Use of targeted next generation sequencing to characterize tumor mutational burden and efficacy of immune checkpoint inhibition in small cell lung cancer. J Immunother Cancer. 2019;7:87.
Choi M, Kipps T, Kurzrock R. ATM mutations in cancer: therapeutic implications. Mol Cancer Ther. 2016;15:1781–1791.
Ding L, Getz G, Wheeler DA, et al. Somatic mutations affect key pathways in lung adenocarcinoma. Nature. 2008;455:1069–1075.
Yin M, Grivas P, Emamekhoo H, et al. ATM/RB1 mutations predict shorter overall survival in urothelial cancer. Oncotarget. 2018;9:16891–16898.