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

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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
Pages (from-to)e720-e729
JournalThe oncologist
Volume24
Issue number8
DOIs
Publication statusPublished - Aug 2019

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Keywords

  • Diffuse large B‐cell lymphoma
  • Direct‐acting antivirals
  • Hepatitis C virus
  • R‐CHOP

Cite this

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., ... Arcaini, L. (2019). Direct-Acting Antivirals in Hepatitis C Virus-Associated Diffuse Large B-cell Lymphomas. The oncologist, 24(8), e720-e729. https://doi.org/10.1634/theoncologist.2018-0331