Interferon-free antiviral treatment in B-cell lymphoproliferative disorders associated with hepatitis C virus infection.
Regression of hepatitis C virus (HCV)-associated lymphoma with interferon (IFN)-based antiviral treatment supports an etiological link between lymphoma and HCV infection. In addition, a favorable impact of antiviral treatment on overall survival of patients with HCV-related lymphoma has been reported. Data on IFN-free regimens combining direct-acting antivirals (DAAs) in HCV-associated lymphoproliferative disorders are scanty. We analyzed the virological and lymphoproliferative disease response (LDR) of 46 patients with indolent B-cell non-Hodgkin lymphomas (NHLs) or chronic lymphocytic leukemia (CLL) and chronic HCV infection treated with DAAs. The histological distribution was 37 marginal zone lymphomas (MZLs), 2 lymphoplasmacytic lymphomas, 2 follicular lymphomas, 4 CLL/small lymphocytic lymphomas (CLL/SLLs), and 1 low-grade NHL not otherwise specified. Thirty-nine patients received a sofosbuvir-based regimen and 7 patients received other DAAs. The median duration of DAA therapy was 12 weeks (range, 6-24 weeks). A sustained virological response at week 12 after finishing DAAs was obtained in 45 patients (98%); the overall LDR rate was 67%, including 12 patients (26%) who achieved a complete response. The LDR rate was 73% among patients with MZL, whereas no response was observed in CLL/SLL patients. Seven patients cleared cryoglobulins out of 15 who were initially positive. After a median follow-up of 8 months, 1-year progression-free and overall survival rates were 75% (95% confidence interval [CI], 51-88] and 98% [95% CI, 86-100], respectively. DAA therapy induces a high LDR rate in HCV-associated indolent lymphomas. These data provide a strong rationale for prospective trials with DAAs in this setting.
Department of Molecular Medicine, University of Pavia, Pavia, Italy.|Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
Luca
0000-0002-9504-991X
L
Arcaini
Assistance Publique-Hôpitaux de Paris Centre Hospitalier Universitaire Bicêtre, Université Paris Sud, INSERM, Le Kremlin-Bicêtre, France.
Caroline
0000-0003-4364-7173
C
Besson
Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Marco
0000-0003-2493-7749
M
Frigeni
Paris 5 Descartes University, INSERM U1213 and Unité mixte de service 20, Institut Pasteur, Department of Hepatology, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
Hélène
0000-0001-6703-369X
H
Fontaine
Department of Hematology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy.
Maria
M
Goldaniga
Division of Clinical Immunology, Sapienza University of Rome, Fondazione Roma, Rome, Italy.
Milvia
0000-0003-1841-6808
M
Casato
Division of Clinical Immunology, Sapienza University of Rome, Fondazione Roma, Rome, Italy.
Marcella
0000-0002-4053-6091
M
Visentini
Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX.
Harrys A
0000-0003-0814-604X
HA
Torres
Department of Hepatology, Centre Hospitalier Universitaire Limoges, U850 INSERM, University of Limoges, Limoges, France.
Veronique
0000-0002-6951-0784
V
Loustaud-Ratti
Department of Internal Medicine 1, Goethe University Hospital, Frankfurt, Germany.
Jan
J
Peveling-Oberhag
Division of Infectious Diseases, Ospedale San Bortolo, Vicenza, Italy.
Paolo
P
Fabris
Department of Infectious Diseases, Ospedale Niguarda Ca' Granda, Milan, Italy.
Roberto
0000-0003-4965-8789
R
Rossotti
Hematology Unit, Centro Trapianti e Terapie Cellulari Carlo Melzi, Dipartimento di Scienze Mediche Sperimentali e Cliniche, Azienda Sanitaria Universitaria Integrata, Udine, Italy.
Francesco
0000-0003-3995-8817
F
Zaja
Department of Hematology Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
Luigi
L
Rigacci
Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
Sara
0000-0002-2682-3414
S
Rattotti
Department of Clinical Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy.|Division of Infectious and Tropical Diseases, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy.
Raffaele
0000-0002-0235-9207
R
Bruno
Division of Hematology, Ospedale di Circolo e Fondazione Macchi, University of Insubria, Varese, Italy.
Michele
0000-0002-0905-5927
M
Merli
Sorbonne Universités, Pierre and Marie Curie University (University of Paris 06), INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (Unité mixte de recherche S1136), Paris, France.
Céline
C
Dorival
Toulouse 3 University, Unité mixte de recherche 152 Institut de Recherche pour le Développement, Department of Internal Medicine and Digestive Diseases, Hôpital Purpan, Toulouse, France.
Laurent
0000-0003-0676-7539
L
Alric
Department of Hepatology, Centre Hospitalier Universitaire Limoges, U850 INSERM, University of Limoges, Limoges, France.
Arnaud
A
Jaccard
Paris 5 Descartes University, INSERM U1213 and Unité mixte de service 20, Institut Pasteur, Department of Hepatology, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France.
Stanislas
0000-0001-9772-9591
S
Pol
Sorbonne Universités, Pierre and Marie Curie University (University of Paris 06), INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (Unité mixte de recherche S1136), Paris, France.|Public Health Department, Assistance Publique-Hôpitaux de Paris, Paris, France.
Fabrice
0000-0002-8672-7918
F
Carrat
Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Virginia Valeria
0000-0003-0130-915X
VV
Ferretti
Department of Cell Therapy and Hematology, Ospedale San Bortolo, Vicenza, Italy.
Carlo
0000-0003-2863-0883
C
Visco
Paris 5 Descartes University, Assistance Publique-Hôpitaux de Paris, Department of Adult Hematology and Imagine Institute, Hôpital Necker, Paris, France; and.|INSERM U1163, Centre National de la Recherche Scientifique Équipes de recherche labellisées 8254, Université Sorbonne Paris Cité, Imagine Institute, Paris, France.
Olivier
O
Hermine
D000998:Antiviral Agents / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000069474:Sofosbuvir / Q000008:administration & dosage*; D015996:Survival Rate
D000998:Antiviral Agents; D000069474:Sofosbuvir