Department of Oncology and Hematology University of Milan, and Azienda SocioSanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy.
Hematology Division, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Blood Cancer J. 2021 Mar 6;11(3):53. doi: 10.1038/s41408-021-00445-z.
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 (JAK2). Givinostat, a histone-deacetylase inhibitor that selectively targets JAK2 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.
真性红细胞增多症(PV)是一种 BCR-ABL1 阴性骨髓增殖性肿瘤(MPN),其特征是骨髓中红系、髓系和巨核细胞成分过度增殖,主要是由于 JAK2 基因突变(JAK2)。Givinostat 是一种组蛋白去乙酰化酶抑制剂,选择性针对 JAK2 细胞生长,在 3 项 1/2 期临床试验中已证明在 PV 患者中具有良好的疗效和安全性。本文重点介绍了一项开放性、长期研究的 4 年平均(2.8 年中位数)随访结果,该研究共纳入 51 例 PV 患者(共纳入 54 例 MPN 患者),这些患者在之前的研究中或在同情用药中接受过 givinostat 的临床获益,并且在最后一次有效和耐受剂量时继续接受 givinostat。主要目的是确定 givinostat 的长期安全性和耐受性,以及研究者根据国际公认的反应标准评估的疗效。在随访期间,只有 10%的 PV 患者报告了 3 级治疗相关不良事件(AE),而没有患者报告了 4 级或 5 级治疗相关 AE。在 PV 患者的整个随访期间,总体缓解率始终大于 80%。总之,givinostat 在 PV 患者中表现出良好的安全性和疗效,支持在该人群中长期使用。