Direct-Acting Antivirals in Hepatitis C Virus-Associated Diffuse Large B-cell Lymphomas.


Journal

The oncologist
ISSN: 1549-490X
Titre abrégé: Oncologist
Pays: England
ID NLM: 9607837

Informations de publication

Date de publication:
08 2019
Historique:
received: 06 06 2018
accepted: 06 11 2018
pubmed: 16 12 2018
medline: 1 8 2020
entrez: 16 12 2018
Statut: ppublish

Résumé

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. 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 [ 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 ( 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. 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.

Sections du résumé

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 [
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 (
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.

Identifiants

pubmed: 30552159
pii: theoncologist.2018-0331
doi: 10.1634/theoncologist.2018-0331
pmc: PMC6693710
doi:

Substances chimiques

Antiviral Agents 0
Rituximab 4F4X42SYQ6
Vincristine 5J49Q6B70F
Doxorubicin 80168379AG
Cyclophosphamide 8N3DW7272P
Prednisone VB0R961HZT

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e720-e729

Informations de copyright

© AlphaMed Press 2018.

Déclaration de conflit d'intérêts

Disclosures of potential conflicts of interest may be found at the end of this article.

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Auteurs

Michele Merli (M)

Hematology, University Hospital Ospedale di Circolo e Fondazione Macchi-ASST Sette Laghi, University of Insubria, Varese, Italy michele.merli@asst-settelaghi.it.

Marco Frigeni (M)

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

Laurent Alric (L)

Department of Internal Medicine and Digestive Diseases, University Hospital Toulouse, UMR 152 PharmaDev, IRD Toulouse 3 University, France.

Carlo Visco (C)

Cell Therapy and Hematology, Ospedale San Bortolo, Vicenza, Italy.

Caroline Besson (C)

Unit of Hematology-Oncology, Centre Hospitalier de Versailles, Le Chesnay; Université Versailles Saint Quentin en Yvelines; INSERM U1018, Centre pour la Recherche en Epidemiologie et Sante des Populations (CESP), Equipe Generations et Sante, Gustave Roussy, Villejuif, France.

Lara Mannelli (L)

Hematology, Azienda Ospedaliera Careggi, Florence, Italy.

Alice Di Rocco (A)

Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome, Italy.

Angela Ferrari (A)

Hematology Unit, Azienda Unità Sanitaria Locale-IRCCS Reggio Emilia, Italy.

Lucia Farina (L)

Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Mario Pirisi (M)

Translational Medicine, University of Piemonte Orientale UPO, Novara, Italy.

Francesco Piazza (F)

Medicine-Hematology, University of Padova, Padova, Italy.

Véronique Loustaud-Ratti (V)

Hepatology, Centre Hospitalier Universitaire de Limoges, U-1248 INSERM, Université de Limoges, Limoges, France.

Annalisa Arcari (A)

Haematology Unit, Azienda AUSL, Piacenza, Italy.

Dario Marino (D)

Department of Clinical and Experimental Oncology, Veneto Institute of Oncology, IOV IRCCS, Padova, Italy.

Antonello Sica (A)

Oncology and Hematology, AOU "Luigi Vanvitelli", Naples, Italy.

Maria Goldaniga (M)

Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Chiara Rusconi (C)

Hematology and Oncology, Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milan, Italy.

Massimo Gentile (M)

Onco-Hematology, Hematology Unit, AO of Cosenza, Cosenza, Italy.

Emanuele Cencini (E)

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

Francesco Benanti (F)

Infectious Diseases, University of Catania, Catania, Italy.

Maria Grazia Rumi (MG)

Hepatology, Ospedale San Giuseppe IRCCS Multimedica, University of Milan, Milan, Italy.

Virginia Valeria Ferretti (VV)

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

Paolo Grossi (P)

Infectious and Tropical Diseases, University Hospital Ospedale di Circolo e Fondazione Macchi - ASST Sette Laghi, University of Insubria, Varese, Italy.

Manuel Gotti (M)

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

Roberta Sciarra (R)

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

Maria Chiara Tisi (MC)

Cell Therapy and Hematology, Ospedale San Bortolo, Vicenza, Italy.

Isabel Cano (I)

Hematology Department, Centre Hospitalier de Versailles, Versailles, France.

Valentina Zuccaro (V)

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

Francesco Passamonti (F)

Hematology, University Hospital Ospedale di Circolo e Fondazione Macchi-ASST Sette Laghi, University of Insubria, Varese, Italy.

Luca Arcaini (L)

Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Division of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

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