Association of a novel 27-gene immuno-oncology assay with efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer

Harsha Ranganath, Amit L. Jain, Justin R. Smith, Julie Ryder, Amina Chaudry, Emily Miller, Felicia Hare, Poojitha Valasareddy, Robert S. Seitz, David R. Hout, Matthew G. Varga, Brock L. Schweitzer, Tyler J. Nielsen, Janice Mullins, Douglas T. Ross, David R. Gandara, Gregory A. Vidal

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Immune checkpoint inhibitor (ICI) therapies represent a major advance in treating a variety of advanced-stage malignancies. Nevertheless, only a subset of patients benefit, even when selected based on approved biomarkers such as PD-L1 and tumor mutational burden. New biomarkers are needed to maximize the therapeutic ratio of these therapies. Methods: In this retrospective cohort, we assessed a 27-gene RT-qPCR immuno-oncology (IO) gene expression assay of the tumor immune microenvironment and determined its association with the efficacy of ICI therapy in 67 advanced-stage NSCLC patients. The 27-gene IO test score (IO score), programmed cell death ligand 1 immunohistochemistry tumor proportion score (PD-L1 TPS), and tumor mutational burden (TMB) were analyzed as continuous variables for response and as binary variables for one-year progression free survival. The threshold for the IO score was prospectively set based upon a previously described training cohort. Prognostic implications of the IO score were evaluated in a separate cohort of 104 advanced-stage NSCLC patients from The Cancer Genome Atlas (TCGA) who received non-ICI therapy. Results: The IO score was significantly different between responders or non-responders (p = 0.007) and associated with progression-free survival (p = 0.001). Bivariate analysis established that the IO score was independent of PD-L1 TPS and TMB in identifying patients benefiting from ICI therapy. In a separate cohort of late-stage NSCLC patients from TCGA, the IO score was not prognostic of outcome from non-ICI-treated patients. Conclusions: This study is the first application of this 27-gene IO RT-qPCR assay in a clinical cohort with outcome data. IO scores were significantly associated with response to ICI therapy and prolonged progression-free survival. Together, these data suggest the IO score should be further studied to define its role in informing clinical decision-making for ICI treatment in NSCLC.

Original languageEnglish (US)
Article number407
JournalBMC Cancer
Volume22
Issue number1
DOIs
StatePublished - Dec 2022

Keywords

  • Gene expression profiling
  • Immunotherapy
  • Programmed death ligand 1
  • Tumor biomarkers
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

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