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Lymphoma

Interferon-free compared to interferon-based antiviral regimens as first-line therapy for B-cell lymphoproliferative disorders associated with hepatitis C virus infection

Leukemia volume 34, pages 1462–1466 (2020)Cite this article

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The most convincing evidence to support the causal role of hepatitis C virus (HCV) in lymphomagenesis was provided by the observation of the regression of indolent lymphoma after eradication of HCV infection with interferon (IFN)-based antiviral therapy (AT), with a strong correlation between hematological and virological responses [1,2,3], in accordance with the proposed pathogenetic model of chronic antigenic stimulation [4]. However, a direct antiproliferative effect of IFN on malignant lymphocytes could not be ruled out and only IFN-free regimen could provide a definitive evidence of the role of HCV in lymphomagenesis. In the last decade, the therapy for chronic HCV infection has dramatically changed, starting by the identification of the nonstructural proteins and the knowledge about their roles in the viral life cycle, leading to the development of direct-acting antiviral (DAA) drugs [5]. In terms of efficacy, DAA therapy can lead to a sustained virological response (SVR), regarded as a cure, in almost 100% of patients, with a better and safer tolerability profile than IFN treatment [6]. In 2016, we reported a large international survey on 46 pts with HCV-associated indolent B-cell nonHodgkin lymphomas (HCV-B-NHL) treated with an IFN-free AT. We showed that IFN-free AT led, as expected, to an impressive SVR of 98% at week 12, and a hematological overall response rate (ORR) of 67%, including 12 patients (26%) who achieved a complete response (CR) [7].

Optimal treatment for extra-hepatic manifestations of HCV infection is a matter of debate [8]. In order to provide a better guideline for HCV-B-NHL treatment, here we present an analysis of a series of 100 pts, including updated follow-up of previously reported and additional cases with HCV-associated B-cell lymphoproliferative disorders.

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Fig. 1

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Funding

The research leading to these results has received funding from AIRC under IG 2017—ID. 20767 project—P.I. Luca Arcaini and from “Ricerca Corrente Fondazione IRCCS Policlinico San Matteo”—P.I. Luca Arcaini. The ANRS-CO22 HEPATHER cohort was sponsored and funded by ANRS (France REcherche Nord & Sud Sida-HIV Hépatites). The sponsor has not participated in the statistical analysis and interpretation of data, in the writing the manuscript, and in the decision to submit the work for publication.

Author information

Author notes

  1. These authors contributed equally: Marco Frigeni, Caroline Besson

  2. These authors jointly supervised this work: Olivier Hermine, Luca Arcaini

Authors and Affiliations

  1. Department of Molecular Medicine, University of Pavia, Pavia, Italy

    Marco Frigeni, Irene Defrancesco, Virginia Valeria Ferretti & Luca Arcaini

  2. Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Marco Frigeni, Sara Rattotti & Luca Arcaini

  3. APHP CHU Bicêtre, Université Paris Sud, INSERM U1012, Orsay, France

    Caroline Besson

  4. Department of Medicine, Section of Hematology, University of Verona, Verona, Italy

    Carlo Visco

  5. Department of Hepatology, Inserm U-1213 and UMS-20, Institut Pasteur, Paris 5 Descartes University, Paris, France

    Helene Fontaine

  6. Department of Hematology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milano, Italy

    Maria Goldaniga

  7. Department of Translational and Precision Medicine, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy

    Marcella Visentini

  8. Division of Hematology, Department of Translational and Precision Medicine, Sapienza University of Rome, Fondazione Roma, Rome, Italy

    Alessandro Pulsoni

  9. Department of Infectious Diseases, Infection Control, and Employee Health, and Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Harrys A. Torres

  10. Department of Internal Medicine 1, Goethe-University Hospital, Frankfurt, Germany

    Jan Peveling-Oberhag

  11. Department of Internal Medicine 1, Robert-Bosch-Krankenhaus, Stuttgart, Germany

    Jan Peveling-Oberhag

  12. Department of Infectious Diseases, Ospedale Niguarda Ca’ Granda, Milano, Italy

    Roberto Rossotti

  13. Hematology Unit, Azienda Sanitaria Universitaria Integrata, Trieste, Italy

    Francesco Zaja

  14. Hematology Unit and Bone Marrow Transplant Unit, San Camillo Forlanini Hospital, Rome, Italy

    Luigi Rigacci

  15. Division of Hematology, Ospedale di Circolo e Fondazione Macchi, University of Insubria, Varese, Italy

    Michele Merli

  16. Sorbonne Université, INSERM, Institut Pierre Louis d’Épidémiologie et de Santé Publique, F75012, Paris, France

    Céline Dorival

  17. Hematology Department, Institut Universitaire du Cancer de Toulouse-Oncopole (IUCT-O) Toulouse 3 University, Paris, France

    Camille Alric

  18. Hematology and Clincal Immunology Branch, Department of Medecine, University of Padova, Padova, Italy

    Francesco Piazza

  19. Hematology Unit, Department of Onco-Hematology, A.O. of Cosenza, Cosenza, Italy

    Massimo Gentile

  20. Division of Hematology, Azienda USL IRCCS Reggio Emilia, Reggio Emilia, Italy

    Angela Ferrari

  21. Department of Translational Medicine, Università del Piemonte Orientale, Novara, Italy

    Mario Pirisi

  22. Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy

    Luca Nassi

  23. Department of Hematology, Ospedale Niguarda Ca’ Granda, Milano, Italy

    Annamaria Frustaci

  24. Division of Infectious Diseases, University Hospital Policlinico Consorziale, Bari, Italy

    Michele Milella

  25. Division of Hematology, Azienda Ospedaliera Senese, University of Siena, Siena, Italy

    Emanuele Cencini

  26. Department of Clinical Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy

    Raffaele Bruno

  27. Division of Infectious and Tropical Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Raffaele Bruno

  28. AP-HP, Department of Adult Hematology and Imagine Institute, Hôpital Necker, University of Paris, Paris, France

    Olivier Hermine

  29. INSERM U 1163, CNRS ERL 8254, Imagine Institute, Université Sorbonne Paris Cité, Paris, France

    Olivier Hermine

Authors
  1. Marco Frigeni
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  2. Caroline Besson
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  3. Carlo Visco
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  4. Helene Fontaine
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Contributions

MF, LA, OH, and CB designed and supervised the overall conduction of the study; VVF, LA, and MF analyzed the data; MF and LA wrote the paper; M.F. and LA collected the data; MF, CB, CV, HF, MGo, MV, AP, HAT, JPO, RR, FZ, LR, MMe, CD, CA, FP, MGe, AF, MP, LN, SR, AF, MMi, EC, ID, RB, OH, and LA enrolled and cared for the patients; MF, CB, OH, and LA. reviewed the paper and all authors approved the final paper.

Corresponding author

Correspondence to Luca Arcaini.

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Conflict of interest

LA received advisory honoraria from Bayer, Celgene, Gilead, Roche, Sandoz, Verastem and research support from Gilead. HAT is or has been the principal investigator for research grants from Gilead Sciences, Merck & Co., Inc., and Vertex Pharmaceuticals, with all funds paid to MD Anderson. HAT also is or has been a paid scientific advisor for Gilead Sciences, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Vertex Pharmaceuticals, Genentech, Novartis, Astellas Pharma, Pfizer Inc., and Theravance Biopharma, Inc.; the terms of these arrangements are being managed by MD Anderson in accordance with its conflict of interest policies. AP received advisory honoraria from Roche, Merck, Pfyzer, Sandoz, Takeda.

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Frigeni, M., Besson, C., Visco, C. et al. Interferon-free compared to interferon-based antiviral regimens as first-line therapy for B-cell lymphoproliferative disorders associated with hepatitis C virus infection. Leukemia 34, 1462–1466 (2020). https://doi.org/10.1038/s41375-019-0687-2

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