Outcome prediction of diffuse large B-cell lymphomas associated with hepatitis C virus infection: a study on behalf of the Fondazione Italiana Linfomi

Abstract

IntroductionIn recent years, many epidemiological studies have increasingly strengthened the evidence that hepatitis C virus (HCV) is associated not only with indolent B-cell non-Hodgkin lymphomas (NHL), but also with diffuse large B-cell lymphomas (DLBCL). 1 An Italian case-control study reported an even higher association of HCV infection with DLBCL (Odds Ratio (OR) 3.5) with respect to indolent NHL (OR 2.3), suggesting that approximately one out of 20 cases of DLBCL, at least in Italy, may be attributable to HCV.2 Unlike indolent B-NHL, there seems to be no role for antiviral treatment in HCV-positive DLBCL, because lymphoma cells, suffering from additional oncogenic lesions, may not be critically dependent on antigen stimulation. For this reason, unlike their indolent counterpart, HCV-associated DLBCL patients should be treated with conventional immunochemotherapy schemes such as R-CHOP, although concerns remain with regard to the potential risk of hepatotoxicity. 3 The prediction of the prognosis in HCV-positive DLBCL is still a subject for debate. In fact, as previously reported, 4,5 HCV-positive DLBCL patients display specific presentation features with respect to their HCV-negative counterparts, potentially affecting many clinical features included in common prognostic scores (i.e. age, number of extranodal sites, stage). Moreover, many laboratory parameters of common ©2014 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol.2013 The online version of this article has a Supplementary Appendix. Manuscript received on July 9, 2013. Manuscript accepted on November 15, 2013 A specific prognostication score for hepatitis C virus-positive diffuse large B-cell lymphomas is not available. For this purpose, the Fondazione Italiana Linfomi (FIL, Italian Lymphoma Foundation) carried out a multicenter retrospective study on a large consecutive series of patients with hepatitis C virus-associated diffuse large B-cell lymphoma to evaluate the prognostic impact of clinical and virological features and to develop a specific prognostic score for this subset of patients. All prognostic evaluations were performed on 535 patients treated with an anthracycline-based induction regimen (with rituximab in 255 cases). Severe hepatotoxicity was observed in 14% of patients. The use of rituximab was not associated with increased rate of severe hepatotoxicity. Three-year overall survival and progression-free survival were 71% and 55%, respectively. At multivariate analysis, ECOG performance status of 2 or over, serum albumin below 3.5 g/dL and HCV-RNA viral load over 1000 KIU/mL retained prognostic significance. We combined these 3 factors in a new "HCV Prognostic Score" able to discriminate 3 risk categories with different overall and progression-free survival (low=0; intermediate=1; high-risk ≥2 factors; P<0.001). This score retained prognostic value in the subgroups of patients treated with and without rituximab (P<0.001).The new score performed better than the International Prognostic Index at multivari...

Antiviral therapy is associated with a better survival in patients with hepatitis C virus and B‐cell non‐Hodgkin lymphomas, ANRS HC‐13 lympho‐C study

“…DLBCL patients displayed a good prognosis with 80% of them achieving CR after front-line treatment and 73% of overall survival at 3-years. These results are consistent with those of Merli et al [26] and Ennishi et al [7]. This prognosis seems better than previously reported by our group in HCV positive patients with B-NHL treated in preRituximab era [5].…”

Hepatitis C and Its Relation to B-Cell Lymphoma

“…Severe hepatotoxicity occurred in 14% of patients but was not associated with the use of RTX. 54 A recent prospective study including 45 patients with HCV infection and DLBCL, all treated with R-CHOP, found a 3-year OS of 73%, 55 which is similar to the results found in HCV-negative DLBCL treated with R-CHOP. Antiviral therapy following CT-induced NHL remission permits to achieve a prolonged disease-free survival (P = .038).…”

The NOTCH pathway is recurrently mutated in diffuse large B-cell lymphoma associated with hepatitis C virus infection

“…Recently, the Fondazione Italiana Linfomi (FIL) proposed a new "HCV Prognostic Score" based on 3 risk factors (performance status, albumin level and HCV-RNA viral load), which is able to identify 3 risk categories with different survival, and may be a useful tool to predict the outcome of HCV-positive DLBCL. 35 Considering that only a minority of our patients received rituximab, investigation of larger cohorts of rituximab-treated patients for NOTCH pathway mutations may be of help in integrating this molecular biomarker in a new comprehensive clinicobiological prognostic score useful for the stratification of HCV-positive DLBCL treated in the rituximab era.…”