文章：

长期安全性和有效性研究：givinostat治疗真性红细胞增多症——三项1/2期研究及同情用药项目的4年平均随访

Long-term safety and efficacy of givinostat in polycythemia vera: 4-year mean follow up of three phase 1/2 studies and a compassionate use program

原文发布日期：2021-03-06

DOI: 10.1038/s41408-021-00445-z

类型: Article

开放获取: 是

英文摘要：

Polycythemia vera (PV) is a BCR-ABL1-negative myeloproliferative neoplasm (MPN) characterized by excessive proliferation of erythroid, myeloid, and megakaryocytic components in the bone marrow, mainly due to a Janus kinase 2 gene mutation (JAK2V617F). Givinostat, a histone-deacetylase inhibitor that selectively targets JAK2V617F cell growth, has demonstrated good efficacy and safety in three phase 1/2 studies in patients with PV. This manuscript focuses on the 4-year mean (2.8 year median) follow-up of an open-label, long-term study that enrolled 51 patients with PV (out of a total of 54 with MPN) who received clinical benefit from givinostat in these previous studies or on compassionate use, and who continued to receive givinostat at the last effective and tolerated dose. The primary objectives are to determine givinostat’s long-term safety and tolerability, and efficacy evaluated by the investigators according to internationally recognized response criteria. During follow-up, only 10% of PV patients reported Grade 3 treatment-related adverse events (AEs), while none had Grade 4 or 5 treatment-related AEs. The overall response rate for the duration of follow-up was always greater than 80% in patients with PV. In conclusion, givinostat demonstrated a good safety and efficacy profile in patients with PV, data supporting long-term use in this population.
 

摘要翻译： 

真性红细胞增多症（PV）是一种BCR-ABL1阴性的骨髓增殖性肿瘤（MPN），其特征是骨髓中红系、粒系和巨核细胞成分的过度增殖，主要由于Janus激酶2基因突变（JAK2V617F）引起。Givinostat是一种选择性靶向JAK2V617F细胞生长的组蛋白去乙酰化酶抑制剂，在针对PV患者的三项1/2期研究中已显示出良好的疗效和安全性。本报告重点关注一项开放标签长期研究的平均4年（中位2.8年）随访结果，该研究纳入了51例PV患者（共54例MPN患者），这些患者在此前的研究或同情用药中从givinostat治疗中获得临床获益，并在研究中以末次有效且可耐受的剂量继续接受givinostat治疗。主要研究目的是评估givinostat的长期安全性和耐受性，以及研究者根据国际公认疗效标准评价的疗效。随访期间，仅10%的PV患者报告了3级治疗相关不良事件（AEs），未出现4级或5级治疗相关AEs。在整个随访期间，PV患者的总体缓解率始终保持在80%以上。综上所述，givinostat在PV患者中表现出良好的安全性和有效性，这些数据支持在该人群中的长期使用。

原文链接：

Long-term safety and efficacy of givinostat in polycythemia vera: 4-year mean follow up of three phase 1/2 studies and a compassionate use program