Hematological response to antiviral treatment in 94 patients with indolent B-cell lymphomas associated with hepatitis C virus infection : a study of the Fondazione Italiana Linfomi (FIL)

Introduction: Hematological response after antiviral therapy (AT) is the strongest argument in favourof an oncogenic role of hepatitis C virus (HCV) in non-Hodgkin’s B-cell lymphoma (NHL). A systematic review has shown that a complete remission(CR) is achieved in 75% of cases (Gisbert 2005); this evidence is based on 65 cases from 16 studies, mostly constitued by small series with insufficient follow-up; this inconsistent evidence hampers definitive conclusion on the anti-lymphoma role of AT and the long-term outcome of these pts. Methods: We analysed virological and hematological response of 94 pts with indolent B-NHL and and HCV infection treated with AT (76 as first-line treatment and 18 as second-line after failure of conventional treatments). All pts were characterized by an indolent course of disease not needing immediate conventional anti-lymphoma therapy. 36 pts received interferon (IFN) (in 26 with ribavirin) and 57 received peg-IFN(in 53 plus ribavirin). Results: Histological, virological and hematological features are summarized in Table 1. Six pts discontinued AT for toxicity or absence of virological response; no pt interrupted AT for NHL progression. Of pts treated with AT as first line, 36 (47%) achieved a CR and 23 (30%) a PR while 14 had stable disease; with a median F-UP of 3.3 yrs, median duration of response was 23 mo. A sustained virological response (SVR) was achieved in 59 pts (78%). Of pts treated with AT as second line, 5 (27%) achieved a CR and 9 (50%) a PR; a SVR was achieved in 10 pts (56%). With a median F-UP of 4.3 yrs, median duration of response was 26 mo. Considering the group treated with AT as first line, hematologic response (CR + PR) was highly significantly associated to the achievement of a SVR (p <0.001) while NHL regression did not correlate with the histotype, the HCV genotype (1 vs. 2) and the type of AT (IFN-based vs peg-IFN-based). Elevatedb2-microglobulin and albumin level < 3.5 g/dl were significantly associated with failure of hematological response (respectively p=0.02 and p=0.03). For pts treated with AT as first line 5-yr OS was 94%; 6 pts died (3 for NHL progression, 2 for HCC and 1 for infection). 5-yr PFS was 78%; PFS were significantly longer in pts who underwent peg-IFN-based AT (p=0.001). Conclusions: These data in a large series of pts confirm high rates of lymphoma regression in pts with indolent NHL treated with AT. Despite similar rates of response between IFN and peg-IFN, peg-IFN-based AT seems able to guarantee a better long term control of lymphoma. Lower response rate in second line suggests AT as front-line approach in this setting if an immediate conventional immunochemotherapy program is not needed.