Role of genomic instability in immunotherapy with checkpoint inhibitors

George Yaghmour, Manjari Pandey, Catherine Ireland, Kruti Patel, Sara Nunnery, Daniel Powell, Scott Baum, Eric Wiedower, Lee Schwartzberg, Michael Martin

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Aim: We evaluated whether tumor genome sequencing to detect the number and type of alterations could be used as a valuable biomarker for judging the potential utility of immune checkpoint inhibitors in patients with advanced cancers. Materials and Methods: We identified patients with solid tumors who were treated with checkpoint inibitors and had received commercially available next generation sequencing (NGS). Tumors profiled by Caris Life Sciences, Foundation Medicine and Guardant360 between 2013 and 2015. Patients were divided into 5 quintiles based on mutational load (pathogenic mutations plus variants of undetermined significance). Results: Fifty patients with solid tumors on immunotherapy that had NGS reports available were identified. Top quintile patients had more genomic alterations (median=16.5) than the others (median=2) and had more pathogenic mutations in cell-cycle regulatory genes (100% versus 48%). The overall survival (OS) was significantly superior for patients in the top quintile (722 days) versus the others (432 days). We found no significant difference in progression-free survival (PFS) between the two groups. The objective response rate was numerically higher for the top quintile (50%) vs. others (20%). Programmed cell death protein 1 (PD1) and programmed death-ligand 1 (PDL1) status by immunohistochemistry was not associated with outcomes. Conclusion: The use of immune checkpoint blockade in tumors with higher mutational load was associated with improved OS. Our results suggest that the evaluation of tumor genomes may be predictive of immunotherapy benefit.

Original languageEnglish (US)
Pages (from-to)4033-4038
Number of pages6
JournalAnticancer research
Volume36
Issue number8
StatePublished - Aug 1 2016

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Genomic Instability
Immunotherapy
Neoplasms
Programmed Cell Death 1 Receptor
Genome
cdc Genes
Mutation
Survival
Biological Science Disciplines
Regulator Genes
Disease-Free Survival
Biomarkers
Immunohistochemistry
Medicine
Ligands

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Yaghmour, G., Pandey, M., Ireland, C., Patel, K., Nunnery, S., Powell, D., ... Martin, M. (2016). Role of genomic instability in immunotherapy with checkpoint inhibitors. Anticancer research, 36(8), 4033-4038.

Role of genomic instability in immunotherapy with checkpoint inhibitors. / Yaghmour, George; Pandey, Manjari; Ireland, Catherine; Patel, Kruti; Nunnery, Sara; Powell, Daniel; Baum, Scott; Wiedower, Eric; Schwartzberg, Lee; Martin, Michael.

In: Anticancer research, Vol. 36, No. 8, 01.08.2016, p. 4033-4038.

Research output: Contribution to journalArticle

Yaghmour, G, Pandey, M, Ireland, C, Patel, K, Nunnery, S, Powell, D, Baum, S, Wiedower, E, Schwartzberg, L & Martin, M 2016, 'Role of genomic instability in immunotherapy with checkpoint inhibitors', Anticancer research, vol. 36, no. 8, pp. 4033-4038.
Yaghmour G, Pandey M, Ireland C, Patel K, Nunnery S, Powell D et al. Role of genomic instability in immunotherapy with checkpoint inhibitors. Anticancer research. 2016 Aug 1;36(8):4033-4038.
Yaghmour, George ; Pandey, Manjari ; Ireland, Catherine ; Patel, Kruti ; Nunnery, Sara ; Powell, Daniel ; Baum, Scott ; Wiedower, Eric ; Schwartzberg, Lee ; Martin, Michael. / Role of genomic instability in immunotherapy with checkpoint inhibitors. In: Anticancer research. 2016 ; Vol. 36, No. 8. pp. 4033-4038.
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