title: Antiviral Treatment of HCV-Infected Patients with B-Cell Non-Hodgkin Lymphoma: ANRS HC-13 Lympho-C Study.
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.
authors.affiliation: Department of Internal Medicine and Digestive Diseases, CHU Purpan, UMR 152, IRD Toulouse 3 University, Toulouse, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Alric
authors.affiliation: Université Paris sud Faculté de Médecine Kremlin Bicêtre, AP-HP Hôpital Bicêtre, Le Kremlin-Bicêtre, IMVA INSERM U1184, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Besson
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), Department of Public Health, Hôpital Saint-Antoine, AP-HP, Paris, France.
authors.forename: Nathanael
authors.initials: N
authors.lastname: Lapidus
authors.affiliation: Department of Internal Medicine and Digestive Diseases, CHU Purpan, UMR 152, IRD Toulouse 3 University, Toulouse, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Jeannel
authors.affiliation: Université Paris sud Faculté de Médecine Kremlin Bicêtre, AP-HP Hôpital Bicêtre, Le Kremlin-Bicêtre, IMVA INSERM U1184, Paris, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Michot
authors.affiliation: Paris 6 Pierre et Marie Curie University, UMR 7211, INSERM, UMR S 959, CNRS, UMR 7211, AP-HP, Department of Internal Medicine, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Cacoub
authors.affiliation: Paris 5 Descartes University, AP-HP, Department of Pathology, Hôpital Necker, Paris, France.
authors.forename: Danielle
authors.initials: D
authors.lastname: Canioni
authors.affiliation: Université Descartes, Inserm U-318 Institut Pasteur, AP-HP, Department of hepatology, Hôpital Cochin, Paris, France.
authors.forename: Stanislas
authors.initials: S
authors.lastname: Pol
authors.affiliation: Paris 6 Pierre et Marie Curie University, AP-HP, Department of Biological Hematology and Cytogenetic, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Davi
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), Department of Public Health, Hôpital Saint-Antoine, AP-HP, Paris, France.
authors.forename: Pascaline
authors.initials: P
authors.lastname: Rabiega
authors.affiliation: Department of Hematology IUCT oncopole, CHU, Toulouse, France.
authors.forename: Loic
authors.initials: L
authors.lastname: Ysebaert
authors.affiliation: Department of Internal Medicine and Digestive Diseases, CHU Purpan, UMR 152, IRD Toulouse 3 University, Toulouse, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Bonnet
authors.affiliation: Paris 5 Descartes University, AP-HP, INSERM U 1163, CNRS ERL 8254, Department of Adult Hematology and Imagine Institute, Hôpital Necker, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D016393:Lymphoma, B-Cell / Q000150:complications* / Q000175:diagnosis; D018442:Lymphoma, B-Cell, Marginal Zone / Q000150:complications; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011092:Polyethylene Glycols / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011480:Protease Inhibitors / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011480:Protease Inhibitors; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a