Pushing the Margin: Advancing Toward an Interferon-Free Strategy in Marginal Zone Lymphoma in Patients With Underlying HCV

Abstract

A 55 year old man with recently diagnosed stage IV-B nodal marginal zone lymphoma (NMZL) based on bone marrow biopsy presented for evaluation of a painful rash of his lower extremities. The patient had a history of HCV genotype 1a with previous non-response to interferon (IFN) and ribavirin and was referred for potential retreatment of HCV. Physical exam was notable for lower extremities with tender purpuric rash with central ulceration and oozing of serosanguinous fluid. Laboratory testing revealed a WBC of 3.06 K/mm3, Hb of 8.7 gm/dL, and platelets of 627 K/mm3. Basic metabolic panel and hepatic panel were normal. HCV PCR was 140,000 IU/mL. Serum was positive for cryoglobulins. CT imaging showed right supraclavicular, mediastinal, and bilateral inguinal lymphadenopathy, as well as splenomegaly. Given the previously reported association between NMZL and HCV cryoglobulinemia, the patient was begun on treatment with ledipasvir 90 mg and sofosbuvir 400 mg without ribavirin for an anticipated 12 week course of therapy. Four weeks into his therapy his HCV PCR was undetectable and he was started on weekly infusions with rituximab for treatment of his NMZL. Eight weeks after starting his HCV therapy, a restaging CT imaging showed resolved adenopathy and unchanged splenomegaly. During treatment, his liver tests remained normal, and his anemia (11.1 gm/dL) and lower extremity lesions improved. He tolerated 12 weeks of ledipasvir/sofosbuvir without complications and achieved sustained virological response. He has no signs of recurrent disease NMZL or HCV at 6 months. Marginal Zone Lymphomas (MZL) are clonal proliferations of B-cells arising from the marginal zone of the secondary lymphoid follicle. MZL has been well associated with chronic infection, including hepatitis C with and without associated cryoglublinemia. There have been several case series demonstrating that eradicating the underlying hepatitis C viremia with IFN and ribavirin can induce MZL (splenic and nodal subtypes) remission. Patients with hepatitis C are now being treated with IFN free, directly acting antiviral therapies (DAA) which have more tolerable side effect profiles and increased efficacy. This case is one of the first reports of the use of DAA therapy for treatment of HCV associated NMZL, with or without adjunct chemotherapy with rituximab. Our case demonstrates that the treatment of HCV with an IFN-free DAA regimen can induce remission in patients with concurrent MZL and is an easier to tolerate alternative to IFN and ribavirin based regimens.