Efficacy and safety of new direct antiviral agents in hepatitis C virus–infected patients with diffuse large B‐cell non‐Hodgkin's lymphoma

Abstract

The association of hepatitis C virus (HCV) with non-Hodgkin's lymphoma (NHL) has been demonstrated throughout the world. The new interferon-free direct antiviral agents (DAAs) showed high efficacy and safety, and preliminary data seem to confirm their activity on low-grade NHL. The question arises as whether or not-and how-to treat the HCV-positive patients suffering from diffuse large B-cell lymphomas (DLBCLs). The aim of this observational study was to evaluate whether DAA antiviral treatment of DLBCL/HCV-infected patients in concomitance with chemotherapy is a safe and effective option. Twenty (13 males and 7 females) HCV genotype 1b-positive subjects, undergoing chemotherapy for DLBCL, were enrolled between June 2015 and December 2015. After informed consent, all patients underwent antiviral therapy (AVT) with sofosbuvir/ledipasvir and chemotherapy (14 rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone and 6 cyclophosphamide, doxorubicin, vincristine, and prednisone) for DLBCL. Complete hematological (Revised European-American Lymphoma classification, Ann Arbor, and International Prognostic Index [IPI] scores) and hepatological (viral markers, liver stiffness, and biochemical parameters) evaluations were made. A historical retrospective cohort of 101 DLBCL/HCV-positive patients not undergoing AVT was enrolled for comparison. DAA-treated and untreated patients were similar for sex distribution, IPI score, and NHL stage, and differed for age (older in treated), chemotherapy and use of AVT. Overall survival (OS) and disease-free survival (DFS) were evaluated among a 52-week of follow-up. No statistical difference was found in OS after 52 weeks (P 5 0.122), whereas a statistically significant higher DFS was achieved in treated patients (P 5 0.036). At the multivariate analysis, only IPI score and AVT were independently correlated with a better DFS. No differences in adverse events were reported. Conclusion: DAA treatment in concomitance with chemotherapy was shown to be safe and effective in influencing remission of aggressive lymphomas in HCV patients. (HEPATOLOGY 2018;67:48-55). SEE EDITORIAL ON PAGE 4I n the last 20 years, the treatment of (HCV)-related chronic hepatitis saw the development of multiple different therapeutic regimens, with an increase of their efficacy overtime. The most recent treatments with direct antiviral agents (DAAs) are the extraordinary peak of this scientific progress, with 80%-100% of patients experiencing sustained virological response (SVR) to the therapy, depending on the stage of the disease and the virus genotype.

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

“…Concerning concurrent DAAs and I-CT administration, none of the nine patients included in our study progressed or died at a median follow-up of 1.6 years (2-year OS and PFS of 100%), in line with remarkable results recently reported by Persico et al with the same concurrent approach [17].…”

“…The study demonstrated that HCV eradication with appropriate approved DAA regimens is feasible and also successful in a challenging population as HCV-positive DLBCL patients treated with I-CT, showing an SVR rate approaching 100% in all genotypes and negligible toxicity (no grade 3-4 AEs, few manageable grade 1-2 AEs, mainly related to RBV). Moreover, although on a small number of patients, we confirmed the absence of significant toxicity issues attributable to DAAs themselves or unexpected drug-drug interactions in patients treated concurrently with different widely adopted DAA regimens and I-CT, confirming the findings of the recently published pilot study evaluating contemporary administration of LDV-SOF and R-CHOP [17]. Compared to sequential strategy, the concurrent treatment with DAAs and I-CT exhibited the inherent advantage to be capable to prevent severe hepatic toxicity related to I-CT-induced HCV-RNA flares.…”

“…This strategy may present the advantage of potentially preventing the development of severe hepatic toxicity, reported to be as high as 27% during R‐CHOP administration . A recently published pilot prospective experience on 14 patients with newly diagnosed genotype 1b HCV‐positive DLBCL, treated with LDV‐SOF concurrently with R‐CHOP, confirmed the comprehensive safety and the potential additional value in terms of the efficacy of this strategy (1‐year DFS and OS of 95%) .…”

Hepatitis B and C virus infection and risk of haematological malignancies

“…A sustained virological response and a lymphoproliferative disease response were obtained in 98% and 67%, respectively, of 45 patients with indolent B‐cell NHLs after completing a course of DAA therapy . Only few, but encouraging, studies have been published on DAA therapy in patients with B‐cell non‐Hodgkin lymphoma …”

Treatment of the extrahepatic manifestations of chronic hepatitis C infection

“…Due to a lack of solid evidence of IFN‐free DAA regimens, the IFN‐based regimen can be considered in patients with NHL. Recent evidence shows that patients with DAA regimens also significantly improved in clinical outcomes, higher SVR rates, and prolonged disease‐free survival after NHL remission …”