Masarova Lucia, Mascarenhas John, Rampal Raajit, Hu Wilson, Livingston Robert A, Pemmaraju Naveen
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Division of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Cancer. 2025 Jan 1;131(1):e35661. doi: 10.1002/cncr.35661. Epub 2024 Dec 1.
The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib was approved by the US Food and Drug Administration in 2014 for treatment of patients with polycythemia vera (PV) who have an inadequate response to or intolerance of hydroxyurea (HU). PV is a chronic myeloproliferative neoplasm defined by primary absolute erythrocytosis, bone marrow hypercellularity, and JAK mutations such as JAK2V617F. Patients with PV experience burdensome symptoms and are at risk of thromboembolic events, in particular those with resistance to or intolerance of initial treatments such as HU. Other risks for patients with PV include progression of disease to more aggressive forms with worse prognoses, such as myelofibrosis or blast-phase myeloproliferative neoplasms. This review summarizes the efficacy and safety of ruxolitinib from key phase 2 and 3 trials (MAJIC-PV, RESPONSE, RESPONSE-2, RELIEF, and Ruxo-BEAT), large real-world studies, and a decade of postmarketing surveillance safety data. The authors focus on improved blood count control, rates of thromboembolic events, symptom improvement, and markers of disease modification such as reduction of JAK2V617F allele burden in patients treated with ruxolitinib. They also discuss the well-characterized safety profile of ruxolitinib regarding hematologic and other adverse events of interest. In the 10 years since its approval, ruxolitinib remains a safe and effective standard-of-care treatment for PV. As the treatment landscape for PV continues to evolve in the coming years, the efficacy and safety profiles of ruxolitinib suggest it will remain a preferred treatment as monotherapy and as a potential backbone of future combination regimens.
口服Janus激酶(JAK)1/JAK2抑制剂芦可替尼于2014年获美国食品药品监督管理局批准,用于治疗对羟基脲(HU)反应不佳或不耐受的真性红细胞增多症(PV)患者。PV是一种慢性骨髓增殖性肿瘤,其特征为原发性绝对红细胞增多、骨髓细胞增多以及JAK突变,如JAK2V617F。PV患者会出现令人困扰的症状,并有发生血栓栓塞事件的风险,尤其是那些对初始治疗(如HU)耐药或不耐受的患者。PV患者的其他风险包括疾病进展为预后更差的侵袭性更强的形式,如骨髓纤维化或急变期骨髓增殖性肿瘤。本综述总结了芦可替尼在关键的2期和3期试验(MAJIC-PV、RESPONSE、RESPONSE-2、RELIEF和Ruxo-BEAT)、大型真实世界研究以及十年上市后监测安全数据中的疗效和安全性。作者重点关注接受芦可替尼治疗的患者在血细胞计数控制改善、血栓栓塞事件发生率、症状改善以及疾病改善标志物(如JAK2V617F等位基因负担降低)方面的情况。他们还讨论了芦可替尼在血液学及其他相关不良事件方面已明确的安全性。自获批以来的10年里,芦可替尼仍然是PV安全有效的标准治疗药物。随着未来几年PV治疗格局的不断演变,芦可替尼的疗效和安全性表明它仍将是单药治疗的首选药物以及未来联合治疗方案的潜在基础。