Division of Hematology and Medical Oncology, Mayo Clinic Cancer Center, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ, 85259, USA.
Curr Hematol Malig Rep. 2013 Dec;8(4):325-32. doi: 10.1007/s11899-013-0178-x.
The landscape of therapy for myelofibrosis (MF) is evolving at a pace not previously seen for this clonal myeloproliferative neoplasm. The discovery of the JAK2 V617F mutation in 2005 has led to the rapid development of therapy specifically developed for afflicted MF patients. Indeed, the successful phase III studies of ruxolitinib demonstrating improved symptomatic burden, splenomegaly and survival led to the first approved myelofibrosis drug in the United States and Europe. Multiple additional JAK2 inhibitors are currently in or nearing phase III testing, including SAR302503 (fedratinib), SB1518 (pacritinib) and CYT387 (momelotinib), seeking to offer incremental benefits to ruxolitinib in regards to cytopenias or other disease features. In parallel, phase III testing of pomalidomide is ongoing, with the goal of solidifying the role of immunomodulatory therapy in MF-associated anemia. Multiple single agents strategies are ongoing with histone deacetylase inhibitors, hedgehog inhibitors and hypomethylation agents. Incremental advances are further sought, either in additive or synergistic fashion, from combination strategies of ruxolitinib with multiple different approaches ranging from allogeneic stem cell transplant to current therapies mitigating anemia and further impacting the bone marrow microenvironment or histology. Transitioning from a pre-2011 era devoid of approved MF therapies to one of multiple agents that target not only disease course but symptomatic burden has indeed changed the platform from which MF providers are able to launch individualized treatment plans. In this article, we discuss the diagnostic and therapeutic milestones achieved through MF research and review the emerging pharmacologic agents on the treatment horizon.
骨髓纤维化（MF）的治疗格局正在以前所未有的速度发展，这在这种克隆性骨髓增生性肿瘤中从未出现过。2005 年发现 JAK2 V617F 突变后，专门为受影响的 MF 患者开发的治疗方法迅速发展。事实上，ruxolitinib 的成功 III 期研究表明，症状负担、脾肿大和生存率得到改善，导致美国和欧洲批准了第一种骨髓纤维化药物。目前，还有多种其他 JAK2 抑制剂正在进行或接近 III 期测试，包括 SAR302503（fedratinib）、SB1518（pacritinib）和 CYT387（momelotinib），旨在为 ruxolitinib 在血细胞减少症或其他疾病特征方面提供额外的益处。与此同时，pomalidomide 的 III 期测试正在进行中，旨在巩固免疫调节疗法在 MF 相关贫血中的作用。多种单药策略正在进行中，包括组蛋白去乙酰化酶抑制剂、 hedgehog 抑制剂和低甲基化剂。正在寻求进一步的增量进展，无论是通过与多种不同方法的组合策略（从同种异体干细胞移植到目前减轻贫血并进一步影响骨髓微环境或组织学的治疗方法）以相加或协同的方式。从缺乏批准的 MF 治疗方法的 2011 年前时代过渡到针对疾病过程和症状负担的多种药物时代，确实改变了 MF 提供者能够启动个体化治疗计划的平台。在本文中，我们讨论了通过 MF 研究取得的诊断和治疗里程碑，并回顾了治疗前景中新兴的药物。
