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

The oncologist

article

Michele Merli¹  Mario Pirisi²  Francesco Piazza³  Véronique Loustaud-Ratti⁴  Annalisa Arcari⁵  Dario Marino⁶  Antonello Sica⁷  Maria Goldaniga⁸  Chiara Rusconi⁹  Massimo Gentile^1,10  Emanuele Cencini^1,11  Marco Frigeni^1,12  Francesco Benanti^1,13  Maria Grazia Rumi^1,14  Virginia Valeria Ferretti^1,12  Paolo Grossi^1,15  Manuel Gotti^1,16  Roberta Sciarra^1,16  Maria Chiara Tisi^1,17  Isabel Cano^1,18  Valentina Zuccaro^1,19  Francesco Passamonti¹  Laurent Alric^2,20  Luca Arcaini^1,12  Carlo Visco^1,17  Caroline Besson^2,21  Lara Mannelli^2,24  Alice Di Rocco^2,25  Angela Ferrari^2,26  Lucia Farina^2,27 

[1] University Hospital Ospedale di Circolo e Fondazione Macchi–ASST Sette Laghi, University of Insubria;Translational Medicine, University of Piemonte Orientale UPO;Medicine-Hematology, University of Padova;Centre Hospitalier Universitaire de Limoges, Université de Limoges;Haematology Unit;Department of Clinical and Experimental Oncology, Veneto Institute of Oncology;Oncology and Hematology;Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico;Niguarda Cancer Center, Ospedale Niguarda Ca' Granda;Hematology Unit;Azienda Ospedaliera Senese, University of Siena;Department of Molecular Medicine, University of Pavia;University of Catania;Ospedale San Giuseppe IRCCS Multimedica, University of Milan;University Hospital Ospedale di Circolo e Fondazione Macchi - ASST Sette Laghi, University of Insubria;Division of Hematology;Ospedale San Bortolo;Hematology Department, Centre Hospitalier de Versailles;University of Pavia;Department of Internal Medicine and Digestive Diseases, University Hospital Toulouse, IRD Toulouse 3 University;Unit of Hematology–Oncology, Centre Hospitalier de Versailles;Université Versailles Saint Quentin en Yvelines;Centre pour la Recherche en Epidemiologie et Sante des Populations (CESP);Azienda Ospedaliera Careggi;Sapienza University of Rome;Hematology Unit, Azienda Unità Sanitaria Locale–IRCCS Reggio Emilia;Fondazione IRCCS Istituto Nazionale dei Tumori

关键词: Diffuse large B-cell lymphoma;    Hepatitis C virus;    Direct-acting antivirals;    R-CHOP;   

DOI  :  10.1634/theoncologist.2018-0331

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

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.

【 授权许可】

CC BY|CC BY-NC