Interferon-free antiviral treatment in B-cell lymphoproliferative disorders associated with hepatitis C virus infection

Regression of hepatitis C virus (HCV)-associated lymphoma with interferon-based antiviral treatment supports an etiological link between lymphoma and HCV infection. In addition, a favorable impact of antiviral treatment on overall survival of patients with HCV-related lymphoma has been reported. Data on IFN-free regimens combining direct-acting antivirals (DAAs) in HCV-associated lymphoproliferative disorders are scanty. We analyzed virological and lymphoproliferative disease response (LDR) of 46 patients with indolent B-cell non-Hodgkin lymphomas (NHL) or chronic lymphocytic leukemia (CLL) and chronic HCV infection treated with DAAs. Histological distribution was: 37 marginal zone lymphomas (MZL), 2 lymphoplasmacytic lymphomas, 2 follicular lymphomas, 4 CLL/small lymphocytic lymphoma (SLL), 1 low-grade NHL not otherwise specified. Thirty-nine patients received a Sofosbuvir-based regimen and 7 patients other DAAs. Median duration of DAA therapy was 12 weeks (range 6-24 weeks). A sustained virological response at week 12 after finishing DAAs was obtained in 45 patients (98%); overall LDR rate was 67% including 12 patients (26%) achieving a complete response. LDR rate was 73% among patients with MZL while no response was observed in CLL/SLL patients. Seven patients cleared cryoglobulins out of 15 initially positive. After a median follow up of 8 months, 1-year progression-free and overall survival were 75% [95% confidence interval: 51% - 88%] and 98% [86-100%], respectively. DAA therapy induces a high LDR rate in HCV-associated indolent lymphomas. These data provide a strong rationale for prospective trials with DAAs in this setting.