BMC Cancer (Apr 2022)

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

DOI
https://doi.org/10.1186/s12885-022-09470-y
Journal volume & issue
Vol. 22, no. 1
pp. 1 – 10

Abstract

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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.

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