Rapid clearance of HCV-related splenic marginal zone lymphoma under an interferon-free, NS3/NS4A inhibitor-based treatment. A case report

Rossotti, Roberto; Travi, Giovanna; Pazzi, Annamaria; Baiguera, Chiara; Morra, Enrica; Puoti, Massimo

doi:10.1016/j.jhep.2014.09.031

Cited by 63 publications

(56 citation statements)

References 13 publications

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“…Five patients were already reported in the literature [10][11][12] and were included with updated follow-up. Approval for this study, which was based on the use of archival or cohort data, was obtained from the Institutional Review Boards of the participating centers.…”

Section: Study Design and Patientsmentioning

confidence: 99%

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

Arcaini

Besson

Frigeni

et al. 2016

Blood

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160

131

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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.

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Section: Study Design and Patientsmentioning

confidence: 99%

“…11,12 In this study, we have evaluated the virological and lymphoproliferative disease response (LDR) rates and toxicity of DAAs in a large series of patients with indolent lymphoproliferative disorders treated by DAAs in the absence of immunochemotherapy.…”

Section: Introductionmentioning

confidence: 99%

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

Arcaini

Besson

Frigeni

et al. 2016

Blood

Self Cite

160

131

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“…Data on new IFN-free regimens with direct-acting antivirals in HCV-associated lymphoproliferative disorders are based on clinical reports and they describe rapid response. 106 Because antiviral treatment has a favorable impact on the outcome of HCV-infected NHL patients, 105,107 it should be considered the first option for HCV-associated SMZL if cytoreductive treatment is not immediately necessary.…”

Section: Hcv Infection and Antiviral Treatmentmentioning

confidence: 99%

Splenic marginal zone lymphoma: from genetics to management

Arcaini

Rossi

Paulli

2016

Blood

140

132

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Splenic marginal zone lymphoma (SMZL) is a rare B-cell malignancy involving the spleen, bone marrow, and frequently the blood. SMZL lymphomagenesis involves antigen and/or superantigen stimulation and molecular deregulation of genes (NOTCH2 and KLF2) involved in the physiological differentiation of spleen marginal zone B cells. Diagnosis requires either spleen histology or, alternatively, the documentation of a typical cell morphology and immunophenotype on blood cells coupled with the detection of intrasinusoidal infiltration by CD20+ cells in the bone marrow. Among B-cell tumors, deletion of 7q and NOTCH2 mutations are almost specific lesions of SMZL, thus representing promising diagnostic biomarkers of this lymphoma. Although the majority of SMZLs show an indolent course with a median survival of approximately 10 years, nearly 30% of patients experience a poor outcome. No randomized trials are reported for SMZL, and few prospective trials are available. A watch-and-wait approach is advisable for asymptomatic patients. Treatment options for symptomatic patients ranges from splenectomy to rituximab alone or combined with chemotherapy. In some geographic areas, a subset of patients with SMZL associates with hepatitis C virus infection, prompting virus eradication as an effective lymphoma treatment. It would be worthwhile to explore deregulated cellular programs of SMZL as therapeutic targets in the future; improved clinical and biological prognostication will be essential for identifying patients who may benefit from novel approaches.

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“…A case report 61 recorded the efficacy of 16-week IFN-free treatment combining the NS3/NS4 inhibitor faldaprevir with the nonnucleoside NS5B inhibitor deleobuvir and with ribavirin in a genotype 1 HCV-infected patient with SLVL. After a rapid virologic response (HCV RNA undetectable at week 4) without relevant side effects, a reduction in the lymphocyte counts was observed, and the spleen size returned to normal.…”

Section: New Ifn-free Antiviral Therapiesmentioning

confidence: 99%

“…The 1-year follow-up showed a maintained SVR and a persistence of clonal circulating lymphocytes, but no splenomegaly and other clinical manifestations of lymphoma. 61 A very recent retrospective work by Arcaini et al 62 reported data based on 42 HCV-infected patients with NHL (including 37 MZL) and 4 with chronic lymphocytic leukaemia who received IFN-free treatment (mostly sofosbuvir based), for a median duration of 12 weeks. The overall haematologic response rate was 67%, with 26% of complete response.…”

Section: New Ifn-free Antiviral Therapiesmentioning

confidence: 99%

Hepatitis C and Its Relation to B-Cell Lymphoma

2017

Lymphoma and Chronic Lymphocytic Leukemias

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Hepatitis C virus (HCV) infection is a global health concern, with millions of people chronically infected. The course of this chronic disease may lead to lymphoproliferative disorders ranging from benign mixed cryoglobulinemia to malignant non-Hodgkin lymphoma (NHL). In this article, we reviewed the current knowledge of the different pathologic mechanisms involved in the occurrence of HCV-related lymphoproliferative diseases. Hepatitis C virus directly or indirectly causes different steps of progressive alterations. A chronic antigenic stimulation will select a B-cell clone that will gain immortality via alterations in coding DNA in proto-oncogenes and tumoursuppressor regions. The main challenge in the treatment of HCV-induced NHL is to obtain a sustained virologic response before HCV induced irreversible damages leading to everlasting cell survival. The new interferon-free therapies introduce a new era of management of HCV-NHL, with recent published data to be promising. Nevertheless, further studies are required to assess the safety of those drugs, particularly in association with chemotherapy.

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Rapid clearance of HCV-related splenic marginal zone lymphoma under an interferon-free, NS3/NS4A inhibitor-based treatment. A case report

Cited by 63 publications

References 13 publications

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

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

Splenic marginal zone lymphoma: from genetics to management

Hepatitis C and Its Relation to B-Cell Lymphoma

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