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

BMC Cancer

David R. Gandara¹  Justin R. Smith²  Felicia Hare²  Gregory A. Vidal²  Poojitha Valasareddy²  Emily Miller²  Harsha Ranganath²  Amit L. Jain²  Amina Chaudry²  Matthew G. Varga³  Tyler J. Nielsen³  Robert S. Seitz³  Brock L. Schweitzer³  David R. Hout³  Douglas T. Ross³  Janice Mullins⁴  Julie Ryder⁴ 

[1] Department of Internal Medicine, UC Davis Medical Center;Division of Hematology/Oncology, University of Tennessee Health Sciences Center;Oncocyte Corporation;West Cancer Center and Research institute;

关键词: Tumor biomarkers;    Immunotherapy;    Gene expression profiling;    Programmed death ligand 1;    Tumor microenvironment;   

DOI  :  10.1186/s12885-022-09470-y

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown