Antiviral Treatment of HCV-Infected Patients with B-Cell Non-Hodgkin Lymphoma: ANRS HC-13 Lympho-C Study

PLoS One. 2016 Oct 17;11(10):e0162965. doi: 10.1371/journal.pone.0162965. eCollection 2016.

Abstract

Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders and B-cell non-Hodgkin lymphomas (B-NHLs). Evaluation of the efficacy and safety profiles of different antiviral therapies in HCV patients with B-NHL is warranted.

Methods: First, we evaluated the sustained virologic response (SVR) and safety of Peg-interferon-alpha (Peg-IFN) + ribavirin +/- first protease inhibitors (PI1s) therapy in 61 HCV patients with B-NHL enrolled in a nationwide observational survey compared with 94 matched HCV-infected controls without B-NHL. In a second series, interferon-free regimens using a newly optimal combination therapy with direct-acting antiviral drugs (DAAs) were evaluated in 10 patients with HCV and B-NHL.

Results: The main lymphoma type was diffuse large B-cell lymphoma (38%) followed by marginal zone lymphoma (31%). In the multivariate analysis, patients with B-NHL treated by Peg-IFN-based therapy exhibited a greater SVR rate compared with controls, 50.8% vs 30.8%, respectively, p<0.01, odds ratio (OR) = 11.2 [2.3, 52.8]. B-NHL response was better (p = 0.02) in patients with SVR (69%) than in patients without SVR (31%). Premature discontinuation of Peg-IFN-based therapy was significantly more frequent in the B-NHL group (19.6%) compared with the control group (6.3%), p<0.02. Overall, survival was significantly enhanced in the controls than in the B-NHL group (hazard ratio = 34.4 [3.9, 304.2], p< 0.01). Using DAAs, SVR was achieved in 9/10 patients (90%). DAAs were both well tolerated and markedly efficient.

Conclusions: The virologic response of HCV-associated B-NHL is high. Our study provides a comprehensive evaluation of different strategies for the antiviral treatment of B-NHL associated with HCV infection.

MeSH terms

  • Aged
  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genotype
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification
  • Hepatitis C / complications
  • Hepatitis C / drug therapy*
  • Hepatitis C / mortality
  • Hepatitis C / virology
  • Humans
  • Interferon-alpha / therapeutic use
  • Lymphoma, B-Cell / complications*
  • Lymphoma, B-Cell / diagnosis
  • Lymphoma, B-Cell, Marginal Zone / complications
  • Lymphoma, Large B-Cell, Diffuse / complications
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Polyethylene Glycols / therapeutic use
  • Proportional Hazards Models
  • Protease Inhibitors / therapeutic use
  • RNA, Viral / blood
  • RNA, Viral / metabolism
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use
  • Survival Rate
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Interferon-alpha
  • Protease Inhibitors
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a

Grants and funding

The Lympho-C HC-13 study was promoted and funded by the "Agence Nationale de Recherche sur le Sida et les Hépatites (ANRS) France Recherche Nord Sud Sida-HIV Hépatites.