Abstract LB-212: IMAAGEN study biomarker analysis in patients with long term response to abiraterone acetate with prednisone for non-metastatic castrate resistant prostate cancer
Authors: Chornoguz Olesya , Shen Dong , Kapoor Gurpreet , Li Weimin , Phillips Jennifer , Ryan Charles J. , Crawford E David , Shore Neal D. , Underwood Willie , Taplin Mary-Ellen , Kantoff Philip W. , McGowan Tracy 
Published: August 2018

Abstract
IMAAGEN is a phase 2, multicenter study evaluating 1000 mg abiraterone acetate + 5 mg prednisone (AAP) for the treatment of patients (pts) with high risk non-metastatic castration-resistant prostate cancer (nmCPRC). This study has been ongoing since 2010 and biomarker samples were obtained in 2016 from 30 pts who remained on study and were considered long-term responders (LTRs) with no evidence of progression. To investigate potential biomarkers associated with long-term response, RNA was extracted from whole blood and used for microarray analysis (Clariom D Genechip Expression Array) and Fluidigm qRT-PCR based 38 prostate cancer specific gene expression assay. The gene expression levels for these pts before treatment are not available for comparison. Microarray analysis showed expression of genes crucial for T cell effector function and anti-tumor immune response such as GZMB, GZMK, PRF1, CD3e are expressed at high levels. Pro-inflammatory cytokine expression such as IFNγ and IL-6 is low in these pts, possibly due to prednisone treatment. Expression of known checkpoint molecules that are expressed on T cells such as LAG-3 and PD-1 is uniformly low. Together, high T cell effector gene expression and low T cell checkpoint molecule expression suggests that these pts have T cells capable of enhanced immune surveillance which could prevent metastases. Genes that are crucial for tumor-induced immune-suppression by MDSC or macrophages such PD-L1, A2A receptor, IDO1, iNOS, Arginase, TIGIT and xCT are expressed at low levels in all 30 pts. Furthermore, known markers for granulocytic MDSC (G-MDSC) such as CD15, Arginase are expressed at a low level suggesting that there may be few G-MDSC in the blood of these pts. Accumulation of G-MDSC in the blood of prostate cancer pts has been shown to correlate with disease progression. Altogether, low levels of tumor-induced immune suppression concomitant with overall fitness and enhanced effector function of T cells may lead to enhanced immune surveillance and thus prevent metastases. Our qRT-PCR data showed that all LTRs have lower expression of 38 prostate cancer specific genes compared to historical control of pts with metastatic CRPC. No AR-V7, KLK2, KLK3, PITX2, and TMP.ERG expression is detected in any responder. NPY, cortical related gene, shows increased expression in LTRs compared with pts who have confirmed disease progression. This report presents a preliminary novel panel of immune and prostate-cancer specific biomarkers in pts with high-risk nmCPRC and should be further evaluated to see if they can be used for monitoring and predicting clinical response in prostate cancer trials.
Citation Format: Olesya Chornoguz, Dong Shen, Gurpreet Kapoor, Weimin Li, Jennifer Phillips, Charles J. Ryan, E David Crawford, Neal D. Shore, Willie Underwood, Mary-Ellen Taplin, Philip W. Kantoff, Tracy McGowan. IMAAGEN study biomarker analysis in patients with long term response to abiraterone acetate with prednisone for non-metastatic castrate resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-212.