Favourable Outcome of B-Cell Non Hodgkin Lymphomas Associated with Hepatitis C Virus - ANRS HC13 LYMPHO-C Observational Study

Hepatitis C virus (HCV) associated B-cell non-Hodgkin's lymphoma (B-NHL) is a rare entity that constitutes a model of chronic immune stimulation related lymphomas. They are preferentially Marginal Zone Lymphomas (MZL) and Diffuse Large B Cell Lymphoma (DLBCL) subtypes. In order to study the characteristics of HCV-related B-NHL, we pursue a prospective multicentric observational study in France. We present here the characteristics and evolution of the patients included in this study.

Adult patients with a history of HCV associated B-NHL were included in the study. HCV infection was defined by a positive viral load at diagnosis of NHL. Patients with HIV infection were excluded from the study. Each patient was followed every 6 months during 5 years. Data collection included clinical presentation, treatment and evolution of NHL and HCV infection. Pathological and cytological materials were centralized and reviewed by a group of expert hematopathologists, haematologists and immunologists.

The data of the 64 consecutive patients included between nov 2006 and march 2010 in 20 centers are presented. Median age is 62 years (ranging from 39 to 87 years). There is a predominance of men: sex ratio 1.37 (m37/f27). HCV genotypic distribution does not differ from expected in France: 1: 52% (30/56), 2: 25% (14), 3: 11% (6), 4: 12% (7), 7 missing data.

Twenty-six cases were included at diagnosis of B-NHL, 33 during follow-up of NHL and 5 at relapse. The median interval between NHL diagnosis and last follow-up is 22 months (range 0–152). The histological subtype distribution is DLBCL 39% (22), MZL 37% (21), FL 16% (9), CLL 4% (2), mantle cell lymphoma 4% (2). Remarkably, there is a continuum between MZL and DLBCL, with 6 cases with ongoing transformation. Eight cases are not classified due to small disease infiltration or lack of material. Expert review led to reclassification in few cases from DLBCL to MZL and from FL to MZL.

Among the 22 patients with DLBCL, 3 have no follow-up. The median follow-up of the remaining 19 patients is 21 months. Those patients were treated with polychemotherapy combined with rituximab (R) in all cases except one. Treatment was followed by long lasting complete remission (CR) in all cases except three: a 59 y woman relapsed after Richter syndrome following CLL, a 85 y man progressed on therapy and a 40 y woman with liver DLBCL was resistant to 3 lines of R-chemotherapy. These three patients died from disease progression. During follow-up, 9 patients were treated with antiviral treatment followed by virologic response in all cases but one.

The 21 patients with MZL are 8 splenic MZL including one with transformed DLBCL, 7 nodal MZL, 3 extra-nodal, and 3 Waldenstrom macroglobulinemia; 15 out of 19 cases were associated with positive rheumatoid factor (RF) and/or cryoglobulinemia. Two patients had no follow-up. The median follow-up of the remaining 19 patients is 40 months. The efficacy of antiviral treatment alone on HCV-associated MZL was confirmed in 8 patients and had a RF. The other patients were treated with R-chemotherapy (4), R+antiviral (2), R (2), oral chemotherapy (1) or “watch and wait” (1). The patient with splenic high grade transformation was treated by splenectomy alone and is still in CR. During follow-up, one patient relapsed and is currently treated with R-chemotherapy, two patients died including one after progression to DLBCL.

Among the 9 patients with FL, one had no follow-up, 6 long-lasting CR were obtained following R-chemotherapy, one following three lines of treatment. One other CR was obtained following R-antiviral therapy. Three other patients received antiviral therapy during follow-up with efficacy in one case. Among the two patients with mantle cell lymphoma, one had no follow-up, the other one is on long term CR 6 years following first line chemotherapy (R-CHOP/R-DHAP).

This study strengthens the heterogeneity of HCV-related lymphomas and the need for systematic expert review. Overall, these patients have a favourable outcome. Cases with MZL frequently respond to antiviral treatment and one case with FL to R-antiviral. Combined therapy of R- antiviral seems a good option and should be evaluated for low grade lymphomas. Patients with DLBCL should receive R-CHOP therapy and should be referred in hepatology department for antiviral treatment after chemotherapy due to frequent virologic responses and follow up of liver functions.

No relevant conflicts of interest to declare.