Harrison Claire N, Gupta Vikas K, Gerds Aaron T, Rampal Raajit, Verstovsek Srdan, Talpaz Moshe, Kiladjian Jean-Jacques, Mesa Ruben, Kuykendall Andrew T, Vannucchi Alessandro M, Palandri Francesca, Grosicki Sebastian, Devos Timothy, Jourdan Eric, Wondergem Marielle J, Al-Ali Haifa Kathrin, Buxhofer-Ausch Veronika, Alvarez-Larrán Alberto, Patriarca Andrea, Kremyanskaya Marina, Mead Adam J, Akhani Sanjay, Sheikine Yuri, Colak Gozde, Mascarenhas John
Guys & St Thomas' NHS Foundation Trust, Guy's Hospital, London, SE1 9RT, UK.
Department of Medicine, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, M5G 1Z5, Canada.
Future Oncol. 2022 Sep;18(27):2987-2997. doi: 10.2217/fon-2022-0484. Epub 2022 Aug 11.
Myelofibrosis (MF) is a clonal myeloproliferative neoplasm, typically associated with disease-related symptoms, splenomegaly, cytopenias and bone marrow fibrosis. Patients experience a significant symptom burden and a reduced life expectancy. Patients with MF receive ruxolitinib as the current standard of care, but the depth and durability of responses and the percentage of patients achieving clinical outcome measures are limited; thus, a significant unmet medical need exists. Pelabresib is an investigational small-molecule bromodomain and extraterminal domain inhibitor currently in clinical development for MF. The aim of this article is to describe the design of the ongoing, global, phase III, double-blind, placebo-controlled MANIFEST-2 study evaluating the efficacy and safety of pelabresib and ruxolitinib versus placebo and ruxolitinib in patients with JAKi treatment-naive MF. NCT04603495 (ClinicalTrials.gov).
骨髓纤维化（MF）是一种克隆性骨髓增殖性肿瘤，通常与疾病相关症状、脾肿大、血细胞减少和骨髓纤维化有关。患者承受着巨大的症状负担，预期寿命缩短。MF患者目前接受芦可替尼作为标准治疗，但缓解的深度和持久性以及达到临床结局指标的患者百分比有限；因此，存在重大的未满足医疗需求。培拉布瑞西布是一种正在研究的小分子溴结构域和额外末端结构域抑制剂，目前正处于针对MF的临床开发阶段。本文的目的是描述正在进行的全球III期双盲、安慰剂对照MANIFEST-2研究的设计，该研究评估培拉布瑞西布和芦可替尼对比安慰剂和芦可替尼在初治JAKi的MF患者中的疗效和安全性。NCT04603495（ClinicalTrials.gov）
