1. Direct‐Acting Antivirals in Hepatitis C Virus‐Associated Diffuse Large B‐cell Lymphomas
- Author
-
Maria Grazia Rumi, Laurent Alric, Francesco Passamonti, Dario Marino, Virginia Valeria Ferretti, Isabel Cano, Michele Merli, Manuel Gotti, Roberta Sciarra, Maria Chiara Tisi, Paolo Grossi, Véronique Loustaud-Ratti, Angela Ferrari, Alice Di Rocco, Carlo Visco, Maria Goldaniga, Chiara Rusconi, Emanuele Cencini, F. Benanti, Antonello Sica, Massimo Gentile, Marco Frigeni, Luca Arcaini, Lucia Farina, Francesco Piazza, Annalisa Arcari, Valentina Zuccaro, Lara Mannelli, Caroline Besson, Mario Pirisi, Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Università degli Studi di Pavia = University of Pavia (UNIPV), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Ospedale San Bortolo, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Azienda Ospedaliera Careggi, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Azienda Unita` Sanitaria Locale, Azienda Unita` Sanitaria Locale, La Spezia, IRCCS Istituto Nazionale dei Tumori [Milano], University of Piemonte Orientale, Partenaires INRAE, Università degli Studi di Padova = University of Padua (Unipd), Université de Limoges (UNILIM), Azienda Unità Sanitaria Locale di Bologna (AUSL), Veneto Institute of Oncology, IOV - IRCCS, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Ospedale Niguarda Ca' Granda Hospital, Università degli Studi di Siena = University of Siena (UNISI), University of Catania [Italy], Università degli Studi di Milano = University of Milan (UNIMI), Fondazione IRCCS Policlinico San Matteo, Service d’Hématologie et d’Oncologie, Centre Hospitalier de Versailles, Le Chesnay, France, Pagès, Nathalie, University of Insubria, Varese, University of Pavia, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], University of Padova [Padova, Italy], University of Siena (University of Siena), University of Milan, Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)
- Subjects
Male ,Cancer Research ,Sofosbuvir ,Diffuse large B‐cell lymphoma ,Hematologic Malignancies ,[SDV]Life Sciences [q-bio] ,Direct‐acting antivirals ,Hepatitis C virus ,R‐CHOP ,Hepacivirus ,Direct-acting antivirals ,Gastroenterology ,chemistry.chemical_compound ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,030212 general & internal medicine ,Aged, 80 and over ,Dasabuvir ,Incidence ,Hepatitis C ,Diffuse large B-cell lymphoma ,Middle Aged ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,3. Good health ,[SDV] Life Sciences [q-bio] ,[SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences ,Italy ,Oncology ,Vincristine ,R-CHOP ,030220 oncology & carcinogenesis ,Rituximab ,Female ,Lymphoma, Large B-Cell, Diffuse ,medicine.drug ,Ledipasvir ,Adult ,medicine.medical_specialty ,Antiviral Agents ,Disease-Free Survival ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Progression-free survival ,Cyclophosphamide ,Aged ,Retrospective Studies ,business.industry ,Ribavirin ,Hepatitis C, Chronic ,medicine.disease ,chemistry ,Paritaprevir ,Doxorubicin ,Prednisone ,business - Abstract
International audience; Background: International guidelines suggest hepatitis C virus (HCV) eradication by direct-acting antivirals (DAAs) after first-line immunochemotherapy (I-CT) in patients with HCV-positive diffuse large B-cell lymphoma (DLBCL), although limited experiences substantiate this recommendation. Moreover, only a few data concerning concurrent administration of DAAs with I-CT have been reported.Subjects, materials, and methods: We analyzed hematological and virological outcome and survival of 47 consecutive patients with HCV-positive DLBCL treated at 23 Italian and French centers with DAAs either concurrently (concurrent cohort [ConC]: n = 9) or subsequently (sequential cohort [SeqC]: n = 38) to first-line I-CT (mainly rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone [R-CHOP]-like).Results: Median age was 61 years, 89% of patients had stage III/IV, and 25% presented evidence of cirrhosis. Genotype was 1 in 56% and 2 in 34% of cases. Overall, 46 of 47 patients obtained complete response to I-CT. All patients received appropriate DAAs according to genotype, mainly sofosbuvir-based regimens (n = 45). Overall, 45 patients (96%) achieved sustained virological response, 8 of 9 in ConC and 37 of 38 in SeqC. DAAs were well tolerated, with only 11 patients experiencing grade 1-2 adverse events. Twenty-three patients experienced hepatic toxicity (grade 3-4 in seven) following I-CT in SeqC, compared to only one patient in ConC. At a median follow-up of 2.8 years, two patients died (2-year overall survival, 97.4%) and three progressed (2-year progression-free survival, 93.1%).Conclusion: Excellent outcome of this cohort of HCV-positive DLBCL suggests benefit of HCV eradication by DAAs either after or during I-CT. Moreover, concurrent DAAs and R-CHOP administration appeared feasible, effective, and ideally preferable to deferred administration of DAAs for the prevention of hepatic toxicity.Implications for practice: Hepatitis C virus (HCV)-associated diffuse large B-cell lymphomas (DLBCLs) represent a great therapeutic challenge, especially in terms of hepatic toxicity during immune-chemotherapy (I-CT) and long-term hepatic complications. The advent of highly effective and toxicity-free direct-acting antivirals (DAAs) created an exciting opportunity to easily eradicate HCV shortly after or in concomitance with first-line immunochemotherapy (usually R-CHOP). This retrospective international study reports the real-life use of the combination of these two therapeutic modalities either in the concurrent or sequential approach (DAAs after I-CT) in 47 patients. The favorable reported results on long-term outcome seem to support the eradication of HCV with DAAs in all patients with HCV-positive DLBCL. Moreover, the results from the concurrent approach were effective and safe and displayed an advantage in preventing hepatic toxicity during I-CT.
- Published
- 2019
- Full Text
- View/download PDF