Division of Hematology and Medical Oncology, Mayo Clinic , Phoenix, Arizona, USA.
Department of Hematology and Oncology, UT Health Science Center San Antonio MD Anderson Cancer Center , San Antonio, Texas, USA.
Expert Opin Investig Drugs. 2020 Aug;29(8):809-817. doi: 10.1080/13543784.2020.1782886. Epub 2020 Jul 16.
Current treatment for polycythemia vera (PV) is limited and primarily targets thrombosis risk. Agents targeting distinct mechanisms of action within myeloproliferation are undergoing clinical evaluation to optimize efficacy, improve tolerance and augment long term disease complications.
This article reviews the current data from completed early phase clinical trials in PV, either as monotherapy or in combination with the few currently approved agents.
There remains an opportunity in PV management to improve efficacy and decrease risk of disease progression. Evolving data from use of long acting interferons are serving to clarifying the potential front line role of this therapy. JAK2 inhibition has made a significant impact on decreasing morbidity in patients with hydroxyurea resistant/refractory disease. New approaches may soon expand options including histone deactylase inhibitors (HDACi), either as monotherapy or combination therapy, which showed promising activity and symptomatic control of pruritus. Drugs targeting new molecular pathways (mammalian target of rapamycin, insulin receptor substrates 1/2, MDM2 protein) or the iron metabolism pathway are in early phase trial. Further translational studies assessing efficacy, long term complications, survival, and constitutional symptom control could pave a way for future success in PV drug development either as monotherapy or in combination.
目前治疗真性红细胞增多症（PV）的方法有限，主要针对血栓风险。正在进行临床试验评估靶向骨髓增殖不同作用机制的药物，以优化疗效、提高耐受性并减轻长期疾病并发症。
本文综述了已完成的早期临床试验中，单药治疗或联合少数目前批准的药物在 PV 中的现有数据。
在 PV 管理中仍有机会提高疗效并降低疾病进展风险。长效干扰素的应用数据表明，这种疗法可能具有一线治疗的潜力。JAK2 抑制已显著降低了对羟基脲耐药/难治性疾病患者的发病率。新的治疗方法可能很快会扩展选择，包括组蛋白去乙酰化酶抑制剂（HDACi），无论是单药治疗还是联合治疗，都显示出有希望的活性和瘙痒症状的控制。靶向新分子通路（雷帕霉素靶蛋白、胰岛素受体底物 1/2、MDM2 蛋白）或铁代谢通路的药物正在进行早期临床试验。进一步的转化研究评估疗效、长期并发症、生存和体质症状控制，可能为未来 PV 药物开发无论是单药治疗还是联合治疗的成功铺平道路。
