原发性骨髓纤维化（PMF）是最具侵袭性的骨髓增殖性肿瘤，患者需要更多的关注，并且可能需要更早的治疗干预。目前批准的治疗方案仅限于选择性抑制由驱动基因突变和共存基因突变引起的克隆增殖。 Janus 激酶抑制剂被批准用于有症状的高危 PMF 患者。此外，大多数正在进行的临床研究都集中在患有高风险疾病和/或高输血依赖率的患者。早期/低风险 PMF 的最佳治疗仍有待确定，并且需要随机临床试验评估。根据 2 期非随机研究和专家意见，建议对有症状的低风险 PMF 患者使用聚乙二醇干扰素 α。 Ropeginterferon alfa-2b (ropeg) 是新一代聚乙二醇化干扰素疗法，具有良好的药代动力学和安全性，与之前的制剂相比，注射次数更少。这项随机、双盲、安慰剂对照 3 期试验将评估其对“早期/低风险 PMF”患者的疗效和安全性，根据 Dynamic International，“早期/低风险 PMF”定义为纤维化前 PMF 或处于低或中 1 风险的 PMF预后评分系统+。共同主要终点包括临床相关的完整血液学反应和症状终点。次要终点包括无进展或无事件生存、驱动因素或相关共存基因突变的分子反应、骨髓反应和安全性。疾病进展和事件是根据国际工作组标准和已发表的报告定义的。 150 名符合条件的患者将以 2:1 的比例随机分配接受 Ropeg 或安慰剂治疗。设计了盲样样本量重估。 Ropeg 将采用可耐受的、较高起始剂量的方案进行皮下注射。该研究将为治疗早期/低风险 PMF 提供重要数据，而此时迫切需要抗克隆疾病缓解药物。© 2024。作者。

Primary myelofibrosis (PMF) is the most aggressive of the myeloproliferative neoplasms and patients require greater attention and likely require earlier therapeutic intervention. Currently approved treatment options are limited in their selective suppression of clonal proliferation resulting from driver- and coexisting gene mutations. Janus kinase inhibitors are approved for symptomatic patients with higher-risk PMF. Additionally, most ongoing clinical studies focus on patients with higher-risk disease and/or high rates of transfusion dependency. Optimal treatment of early/lower-risk PMF remains to be identified and needs randomized clinical trial evaluations. Pegylated interferon alfa is recommended for symptomatic lower-risk PMF patients based on phase 2 non-randomized studies and expert opinion. Ropeginterferon alfa-2b (ropeg) is a new-generation pegylated interferon-based therapy with favorable pharmacokinetics and safety profiles, requiring less frequent injections than prior formulations. This randomized, double-blind, placebo-controlled phase 3 trial will assess its efficacy and safety in patients with "early/lower-risk PMF", defined as pre-fibrotic PMF or PMF at low or intermediate-1 risk according to Dynamic International Prognostic Scoring System-plus. Co-primary endpoints include clinically relevant complete hematologic response and symptom endpoint. Secondary endpoints include progression- or event-free survival, molecular response in driver or relevant coexisting gene mutations, bone marrow response, and safety. Disease progression and events are defined based on the International Working Group criteria and well-published reports. 150 eligible patients will be randomized in a 2:1 ratio to receive either ropeg or placebo. Blinded sample size re-estimation is designed. Ropeg will be administered subcutaneously with a tolerable, higher starting-dose regimen. The study will provide important data for the treatment of early/lower-risk PMF for which an anti-clonal, disease-modifying agent is highly needed.© 2024. The Author(s).