Alric Laurent, Besson Caroline, Lapidus Nathanael, Jeannel Juliette, Michot Jean-Marie, Cacoub Patrice, Canioni Danielle, Pol Stanislas, Davi Frédéric, Rabiega Pascaline, Ysebaert Loic, Bonnet Delphine, Hermine Olivier
Department of Internal Medicine and Digestive Diseases, CHU Purpan, UMR 152, IRD Toulouse 3 University, Toulouse, France.
Université Paris sud Faculté de Médecine Kremlin Bicêtre, AP-HP Hôpital Bicêtre, Le Kremlin-Bicêtre, IMVA INSERM U1184, Paris, France.
PLoS One. 2016 Oct 17;11(10):e0162965. doi: 10.1371/journal.pone.0162965. eCollection 2016.
Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders and B-cell non-Hodgkin lymphomas (B-NHLs). Evaluation of the efficacy and safety profiles of different antiviral therapies in HCV patients with B-NHL is warranted.
First, we evaluated the sustained virologic response (SVR) and safety of Peg-interferon-alpha (Peg-IFN) + ribavirin +/- first protease inhibitors (PI1s) therapy in 61 HCV patients with B-NHL enrolled in a nationwide observational survey compared with 94 matched HCV-infected controls without B-NHL. In a second series, interferon-free regimens using a newly optimal combination therapy with direct-acting antiviral drugs (DAAs) were evaluated in 10 patients with HCV and B-NHL.
The main lymphoma type was diffuse large B-cell lymphoma (38%) followed by marginal zone lymphoma (31%). In the multivariate analysis, patients with B-NHL treated by Peg-IFN-based therapy exhibited a greater SVR rate compared with controls, 50.8% vs 30.8%, respectively, p<0.01, odds ratio (OR) = 11.2 [2.3, 52.8]. B-NHL response was better (p = 0.02) in patients with SVR (69%) than in patients without SVR (31%). Premature discontinuation of Peg-IFN-based therapy was significantly more frequent in the B-NHL group (19.6%) compared with the control group (6.3%), p<0.02. Overall, survival was significantly enhanced in the controls than in the B-NHL group (hazard ratio = 34.4 [3.9, 304.2], p< 0.01). Using DAAs, SVR was achieved in 9/10 patients (90%). DAAs were both well tolerated and markedly efficient.
The virologic response of HCV-associated B-NHL is high. Our study provides a comprehensive evaluation of different strategies for the antiviral treatment of B-NHL associated with HCV infection.
丙型肝炎病毒(HCV)感染与淋巴增殖性疾病和B细胞非霍奇金淋巴瘤(B-NHL)相关。有必要评估不同抗病毒疗法对合并B-NHL的HCV患者的疗效和安全性。
首先,我们评估了聚乙二醇化干扰素-α(Peg-IFN)+利巴韦林+/-第一代蛋白酶抑制剂(PI1s)疗法在61例纳入全国性观察性调查的合并B-NHL的HCV患者中的持续病毒学应答(SVR)和安全性,并与94例匹配的未合并B-NHL的HCV感染对照进行比较。在第二个系列研究中,我们评估了10例合并HCV和B-NHL的患者使用新型直接抗病毒药物(DAA)优化联合疗法的无干扰素方案。
主要淋巴瘤类型为弥漫性大B细胞淋巴瘤(38%),其次是边缘区淋巴瘤(31%)。多因素分析显示,接受基于Peg-IFN疗法治疗的B-NHL患者的SVR率高于对照组,分别为50.8%和30.8%,p<0.01,比值比(OR)=11.2 [2.3, 52.8]。SVR患者的B-NHL缓解情况更好(p = 0.02)(69%),高于无SVR的患者(31%)。与对照组(6.3%)相比,B-NHL组基于Peg-IFN疗法的提前停药明显更频繁(19.6%),p<0.02。总体而言,对照组的生存率显著高于B-NHL组(风险比=34.4 [3.9, 304.2],p<0.01)。使用DAA时,10例患者中有9例(90%)实现了SVR。DAA耐受性良好且疗效显著。
HCV相关B-NHL的病毒学应答率较高。我们的研究对与HCV感染相关的B-NHL抗病毒治疗的不同策略进行了全面评估。