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

Michele Merli, Marco Frigeni, Laurent Alric, Carlo Visco, Caroline Besson, Lara Mannelli, Alice Di Rocco, Angela Ferrari, Lucia Farina, Mario Pirisi, Francesco Piazza, Véronique Loustaud-Ratti, Annalisa Arcari, Dario Marino, Antonello Sica, Maria Goldaniga, Chiara Rusconi, Massimo Gentile, Emanuele Cencini, Francesco BenantiMaria Grazia Rumi, Virginia Valeria Ferretti, Paolo Grossi, Manuel Gotti, Roberta Sciarra, Maria Chiara Tisi, Isabel Cano, Valentina Zuccaro, Francesco Passamonti, Luca Arcaini

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
JournalOncologist
DOIs
Publication statusPublished - Dec 14 2018

Fingerprint

Lymphoma, Large B-Cell, Diffuse
Hepacivirus
Antiviral Agents
Liver
Genotype
Survival
Vincristine
Prednisone
Doxorubicin
Cyclophosphamide
Disease-Free Survival
Fibrosis
Retrospective Studies
Guidelines

Cite this

Direct-Acting Antivirals in Hepatitis C Virus-Associated Diffuse Large B-cell Lymphomas. / Merli, Michele; Frigeni, Marco; Alric, Laurent; Visco, Carlo; Besson, Caroline; Mannelli, Lara; Di Rocco, Alice; Ferrari, Angela; Farina, Lucia; Pirisi, Mario; Piazza, Francesco; Loustaud-Ratti, Véronique; Arcari, Annalisa; Marino, Dario; Sica, Antonello; Goldaniga, Maria; Rusconi, Chiara; Gentile, Massimo; Cencini, Emanuele; Benanti, Francesco; Rumi, Maria Grazia; Ferretti, Virginia Valeria; Grossi, Paolo; Gotti, Manuel; Sciarra, Roberta; Tisi, Maria Chiara; Cano, Isabel; Zuccaro, Valentina; Passamonti, Francesco; Arcaini, Luca.

In: Oncologist, 14.12.2018.

Research output: Contribution to journalArticle

Merli, M, Frigeni, M, Alric, L, Visco, C, Besson, C, Mannelli, L, Di Rocco, A, Ferrari, A, Farina, L, Pirisi, M, Piazza, F, Loustaud-Ratti, V, Arcari, A, Marino, D, Sica, A, Goldaniga, M, Rusconi, C, Gentile, M, Cencini, E, Benanti, F, Rumi, MG, Ferretti, VV, Grossi, P, Gotti, M, Sciarra, R, Tisi, MC, Cano, I, Zuccaro, V, Passamonti, F & Arcaini, L 2018, 'Direct-Acting Antivirals in Hepatitis C Virus-Associated Diffuse Large B-cell Lymphomas', Oncologist. https://doi.org/10.1634/theoncologist.2018-0331
Merli, Michele ; Frigeni, Marco ; Alric, Laurent ; Visco, Carlo ; Besson, Caroline ; Mannelli, Lara ; Di Rocco, Alice ; Ferrari, Angela ; Farina, Lucia ; Pirisi, Mario ; Piazza, Francesco ; Loustaud-Ratti, Véronique ; Arcari, Annalisa ; Marino, Dario ; Sica, Antonello ; Goldaniga, Maria ; Rusconi, Chiara ; Gentile, Massimo ; Cencini, Emanuele ; Benanti, Francesco ; Rumi, Maria Grazia ; Ferretti, Virginia Valeria ; Grossi, Paolo ; Gotti, Manuel ; Sciarra, Roberta ; Tisi, Maria Chiara ; Cano, Isabel ; Zuccaro, Valentina ; Passamonti, Francesco ; Arcaini, Luca. / Direct-Acting Antivirals in Hepatitis C Virus-Associated Diffuse Large B-cell Lymphomas. In: Oncologist. 2018.
@article{93fff20c94fa46649fa89c70ddf944f7,
title = "Direct-Acting Antivirals in Hepatitis C Virus-Associated Diffuse Large B-cell Lymphomas",
abstract = "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.",
author = "Michele Merli and Marco Frigeni and Laurent Alric and Carlo Visco and Caroline Besson and Lara Mannelli and {Di Rocco}, Alice and Angela Ferrari and Lucia Farina and Mario Pirisi and Francesco Piazza and V{\'e}ronique Loustaud-Ratti and Annalisa Arcari and Dario Marino and Antonello Sica and Maria Goldaniga and Chiara Rusconi and Massimo Gentile and Emanuele Cencini and Francesco Benanti and Rumi, {Maria Grazia} and Ferretti, {Virginia Valeria} and Paolo Grossi and Manuel Gotti and Roberta Sciarra and Tisi, {Maria Chiara} and Isabel Cano and Valentina Zuccaro and Francesco Passamonti and Luca Arcaini",
note = "{\circledC} AlphaMed Press 2018.",
year = "2018",
month = "12",
day = "14",
doi = "10.1634/theoncologist.2018-0331",
language = "English",
journal = "Oncologist",
issn = "1083-7159",
publisher = "Wiley Blackwell",

}

TY - JOUR

T1 - Direct-Acting Antivirals in Hepatitis C Virus-Associated Diffuse Large B-cell Lymphomas

AU - Merli, Michele

AU - Frigeni, Marco

AU - Alric, Laurent

AU - Visco, Carlo

AU - Besson, Caroline

AU - Mannelli, Lara

AU - Di Rocco, Alice

AU - Ferrari, Angela

AU - Farina, Lucia

AU - Pirisi, Mario

AU - Piazza, Francesco

AU - Loustaud-Ratti, Véronique

AU - Arcari, Annalisa

AU - Marino, Dario

AU - Sica, Antonello

AU - Goldaniga, Maria

AU - Rusconi, Chiara

AU - Gentile, Massimo

AU - Cencini, Emanuele

AU - Benanti, Francesco

AU - Rumi, Maria Grazia

AU - Ferretti, Virginia Valeria

AU - Grossi, Paolo

AU - Gotti, Manuel

AU - Sciarra, Roberta

AU - Tisi, Maria Chiara

AU - Cano, Isabel

AU - Zuccaro, Valentina

AU - Passamonti, Francesco

AU - Arcaini, Luca

N1 - © AlphaMed Press 2018.

PY - 2018/12/14

Y1 - 2018/12/14

N2 - 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.

AB - 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.

U2 - 10.1634/theoncologist.2018-0331

DO - 10.1634/theoncologist.2018-0331

M3 - Article

JO - Oncologist

JF - Oncologist

SN - 1083-7159

ER -