Wei Chan Tze, Than Hein, Huang Feng-Ju, Billa Gauri, Lee Lai Heng
MOH Holdings Pte Ltd, Singapore, Singapore.
Department of Haematology, Singapore General Hospital, Singapore, Singapore.
Hematol Oncol. 2025 Mar;43 Suppl 1(Suppl 1):e70053. doi: 10.1002/hon.70053.
Myelofibrosis (MF) is characterized by anemia, constitutional symptoms, hepatosplenomegaly and bone marrow fibrosis, and is associated with poor survival. The janus kinase inhibitor (JAKi) ruxolitinib has been the mainstay of treatment for over a decade. Despite demonstrated symptomatic and quality of life improvement, unmet clinical needs persist. A literature review identified promising novel targeted treatment options in MF using pre-set selection criteria (available Phase 2 or 3 data, minimum enrollment of 50 patients, trial end date within the last 5 years). Available data for novel and approved therapies were extracted, tabulated, and analyzed for clinical relevancy. From an initial shortlist of 48, 16 retained molecules were selected for inclusion. Other JAKi (pacritinib, momelotinib, jaktinib) address treatment-related cytopenia, expanding the therapeutic utility of this class of agents to patients with baseline anemia or thrombocytopenia. Novel candidates exploit multiple molecular pathways, and offer the potential to improve the management of MF-associated cytopenia (imetelstat, pelabresib, navitoclax, selinexor, luspatercept, sotatercept, elritercept, LCL161, bomedemstat) and recover bone marrow fibrosis (imetelstat, pelabresib, navitoclax and bomedemstat). It remains to be seen if these newer agents can induce any remission in MF and enable patients to come off therapy, but the future is beginning to look much brighter.
骨髓纤维化（MF）的特征为贫血、全身症状、肝脾肿大和骨髓纤维化，且与生存率低相关。十多年来，Janus激酶抑制剂（JAKi）鲁索替尼一直是主要治疗药物。尽管已证明其能改善症状和生活质量，但尚未满足的临床需求依然存在。一项文献综述使用预设的选择标准（可用的2期或3期数据、至少招募50名患者、试验结束日期在过去5年内）确定了骨髓纤维化中有前景的新型靶向治疗选择。提取了新型和已批准疗法的可用数据，制成表格并分析其临床相关性。从最初的48个候选药物清单中，挑选出16种保留分子纳入研究。其他JAKi（帕西替尼、莫美替尼、贾克替尼）可解决与治疗相关的血细胞减少问题，将这类药物的治疗效用扩展至基线贫血或血小板减少的患者。新型候选药物利用多种分子途径，有望改善骨髓纤维化相关血细胞减少的管理（imetelstat、帕拉布昔布、维托克拉克斯、塞利尼索、鲁司泊西、索他瑞西、依瑞西普、LCL161、波美德司他）并恢复骨髓纤维化（imetelstat、帕拉布昔布、维托克拉克斯和波美德司他）。这些新型药物能否在骨髓纤维化中诱导缓解并使患者停药还有待观察，但未来看起来开始更加光明了。
