1019P - Evaluation of indoleamine 2,3-dioxygenase expression (IDO), transforming growth factor beta (TGF-β) and interleukin 13 (IL13) expression on clinical outcome in patients with Hodgkin’s lymphoma

Abstract

Background: Nowadays, patients with Hodgkin’s lymphoma (HL) have a high cure rate. However, approximately 20% pts have relapse or progressive disease. The main histological feature in HL is presence by Hodgkin Reed-Sternberg (HRS) cells. HRS cells produce a diversity of cytokines and chemokines. There is still a limited information of prognostic role expression of cytokines in patients with HL. We assessed the impact on clinical outcome of the IDO, TGF- β and IL-13 expression in patients with HL. Methods: 79 patients (pts) with HL were included in this study (median age: 41, range: 18-65 years; males: 26, females: 53). Early stages of HL have 53.3% and 46.7% pts had advanced stages. Patients were treated with ABVD or BEACOPP (14/esc) and radiation therapy. CR/PR was achieved in 86.1% of patients. 13.9% of pts had relapse or disease progression during the therapy. mRNA expression levels of IDO, TGF-β, IL-13 were measured in fresh pre-treatment tumor tissue specimens from HL patients using real-time qPCR analysis. Results: 25 pts (31.6%) had IDO positive expression (IDO+) and 54 (65.4%) pts was IDO negative (IDO-). Multivariate analysis showed that IDO+ expression correlated with worser EFS rate with HRs of 10.7 [95% confidence interval(CI) 0.4–0.6, p = 0.01], especially in 3-years EFS in IDO+ males comparing to IDO+ females (61% vs 71%, p < 0,05). We did not find significant corellation between such signs as B-symptoms, stages, response reate and IDO expression (p = 0.14). Expression of IL13 and TGF was performed in 69 pts. We divided patients in two groups: IL13+ (high expression) vs. IL13- (low expression) and TGF-β+ (positive expression) vs TGF-β-(negative expression). Number of pts with IL13+ were 34 (49.3%) and 35 (50.7%) with IL13-, while 47 pts were TGF-β+ were (68.1%) and 22 pts (31.9) had TGF-β- expression. It was found, that patients with high IL13 expression had worse EFS and OS rate compared to pts with low IL13 expression. 5-year EFS in patients with IL13- was 98% vs 65% in IL13+ (p < 0,05), as well as 5 year OS in IL13- and IL13+ groups was 98% and 87%, respectively (p < 0,05). Patients with TGF-β- expression had better 5-years OS: 99% in pts with TGF-β- vs. 87% TGF-β+ pts (p < 0.05). We also analyzed two groups of double-positive (IDO+/TGF-β +) and double-negative(IDO-/TGF-β-) and three groups of pts with TGF+/IL13+ vs TGF-/IL13- vs TGF+/IL13 as potential prognosis biomarkers. ROC-analysis showed that response rate in pts with IDO-/TGF-β – was higher compared to IDO+/TGF-β + pts (p = 0.0001). 5-years EFS rate was lower in pts from TGF-β +/IL13+ group comparing to TGF-/IL13- and TGF+/IL13- groups and was 63% vs 99% vs 98% respectively (p < 0.05). Conclusions: Our data showed that IDO, TGF-β and IL13 expressions have a role in predicting clinical outcome in pts with HL. Positive expression of IDO, TGF-β and high expression level of IL13 could be considered as a negative prognostic marker. Significantly worser outcome had pts with positive expression of two cytokines comparing with patients, who had only one positive marker. Legal entity responsible for the study: T. Skrypets Funding: None Disclosure: All authors have declared no conflicts of interest.