Antiviral Agent HARVONI® for the Treatment of HCV-associated Indolent B-Cell Lymphoma

Although several epidemiological studies, including our study have been demonstrated the link between HCV and B-cell non-Hodgkin's lymphoma (NHL), the direct evidence of the HCV-associated-NHL remains uncertain. Direct antiviral agents (DAA) have been shown to have a higher cure rate, less side effects, and a shorter duration of therapy for chronic HCV infection. Whether DAA treatment can cure HCV-associated indolent B-cell NHL remains unclear? If yes, a direct evidence of HCV-associated lymphomagenesis will be approved. Because DAAs are more potent and efficient than pegylated (Peg) interferon plus ribavirin and well-tolerated for the treatment of HCV infection, it is reasonable to use DAAs as the frontline treatment for HCV-positive patients with indolent B-cell NHL, such as MZL, LPL, and low-grade FL, who do not require immediate cytoreductive therapy. The aim of this proposal is to assess whether Harvoni® (ledipasvir and sofosbuvir) could eradicate HCV and lead to durable complete remission of HCV-associated indolent B-cell NHL. In the translational part, we will assess the expression pattern of BAFF-related canonical and non-canonical NF-κB signaling molecules by immunohistochemical (IHC) staining, and t(11;18)(q21;q21), and t(14;18)(q32;q21) by fluorescence in situ hybridization (FISH) in pre-treatment tumors samples of patients in prospectively predicting the antiviral responsiveness of HCV-positive indolent B-cell NHLs. The serum cytokines and chemokines, IFN-gamma, TNF-alpha, IL-4, IL-5, IL-6, IL-13 and CXCL13, BAFF level, and HCV RNA load before and after DAA treatment in HCV-associated indolent B-cell NHLs will be examined. The genotype of the HLA class II, and cloning followed by sequences of the VH region of the immunoglobulin gene derived from pre-treatment tumor samples will be assessed.