Prevalence of established and emerging biomarkers of immune checkpoint inhibitor response in advanced hepatocellular carcinoma

Celina Ang, Samuel J. Klempner, Siraj M. Ali, Russell Madison, Jeffrey S. Ross, Eric A. Severson, David Fabrizio, Aaron Goodman, Razelle Kurzrock, James Suh, Sherri Z. Millis

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

The clinical deployment of immune checkpoint inhibitors (ICIs) has created a tandem drive for the identification of biomarkers linked to benefit. Comprehensive genomic profiling was performed to evaluate the frequency of genomic biomarkers of ICI response in 755 patients with advanced hepatocellular carcinoma (HCC). Median age was 62 years' old, 73% were male, 46% had extrahepatic disease, 107 had documented hepatitis C, 96 had hepatitis B and 4 patients were coinfected. Median tumor mutation burden (TMB) was 4 mutations/Mb and only 6 tumors (0.8%) were TMB-high. Out of 542 cases assessed for microsatellite instability (MSI), one (0.2%) was MSI-high and TMB-high. Twenty-seven (4%) patients had POLE/D alterations. One patient had a pathogenic POLE R762W mutation but TMB was 4 mutations/Mb. Forty percent had DNA damage response gene alterations. In a small case series (N=17) exploring the relationship between biomarkers and ICI response, one patient (TMB 15 mutations/Mb, MSI-low) had a sustained complete response to nivolumab lasting > 2 years. Otherwise there were no significant genomic or TMB differences between responders, progressors, and those with stable disease. Overall, markers of genomic instability were infrequent in this cohort. Larger clinically annotated datasets are needed to explore genomic and non-genomic determinants of ICI response in HCC.

Original languageEnglish
Pages (from-to)4018-4025
Number of pages8
JournalOncotarget
Volume10
Issue number40
StatePublished - 1 Jun 2019

Keywords

  • Biomarkers
  • Hepatocellular carcinoma
  • Immunotherapy
  • Tumor mutation burden

Fingerprint

Dive into the research topics of 'Prevalence of established and emerging biomarkers of immune checkpoint inhibitor response in advanced hepatocellular carcinoma'. Together they form a unique fingerprint.

Cite this