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

Abstract

Key Points• Direct-acting antiviral agents are able to induce lymphoma response in patients with HCV-associated indolent nonHodgkin lymphoma.• The highest rate of lymphoma response (73%) was observed in patients with marginal zone lymphoma.Regression of hepatitis C virus (HCV)-associated lymphoma with interferon (IFN)-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 HCVrelated lymphoma has been reported. Data on IFN-free regimens combining direct-acting antivirals (DAAs) in HCV-associated lymphoproliferative disorders are scanty. We analyzed the virological and lymphoproliferative disease response (LDR) of 46 patients with indolent B-cell non-Hodgkin lymphomas (NHLs) or chronic lymphocytic leukemia (CLL) and chronic HCV infection treated with DAAs. The histological distribution was 37 marginal zone lymphomas (MZLs), 2 lymphoplasmacytic lymphomas, 2 follicular lymphomas, 4 CLL/small lymphocytic lymphomas (CLL/SLLs), and 1 low-grade NHL not otherwise specified. Thirty-nine patients received a sofosbuvir-based regimen and 7 patients received other DAAs. The 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%); the overall LDR rate was 67%, including 12 patients (26%) who achieved a complete response. The LDR rate was 73% among patients with MZL, whereas no response was observed in CLL/SLL patients. Seven patients cleared cryoglobulins out of 15 who were initially positive. After a median follow-up of 8 months, 1-year progression-free and overall survival rates were 75% (95% confidence interval [CI], 51-88] and 98% [95% CI, 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.

Direct-acting antiviral agents in the therapy of hepatitis C virus-related mixed cryoglobulinaemia: a single-centre experience

“…Similar observations were reported by Gragnani et al [26] and more extensively by Arcaini et al [35], who studied 46 HCV-positive patients with indolent NHL treated with IFN-free antiviral regimens and achieved SVR12 in 98% of the patients and lymphoproliferative disease response of splenic marginal zone lymphomas in 73% of the patients. On the contrary, NR was reported in patients with chronic lymphocytic leukaemia/SLL.…”

Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection

“…Eradicating hepatitis C infection results in numerous health benefits, including reduced rates of all‐cause mortality, cirrhosis, hepatic decompensation, and HCC . Successful treatment also confers improvement in extrahepatic manifestations of HCV disease, including cryoglobulinemic vasculitis and HCV‐related non‐Hodgkin lymphoma and other lymphoproliferative disorders, as well as improved productivity and quality of life . Given these and other benefits associated with virologic cure, the HCV guidance panel strongly recommends antiviral treatment for all adults with acute or chronic HCV infection (except those with a short life expectancy that cannot be remediated).…”

The spectrum of MALT lymphoma at different sites: biological and therapeutic relevance

“…Importantly, the strongest evidence for a causal relationship between HCV and lymphoma comes again from the observation of lymphoma regression after antiviral treatment. 68,105,106 Several potential pathogenic mechanisms have been advanced to explain a causative link with lymphoma growth 68,107 : a nondirect antigen-driven stimulation; a direct oncogenic role of HCV; a viral immunosuppressive effect on the tumor cells; and the co-infection by another unknown oncogenic virus.…”