■在过去十年中,真性红细胞增多症(PV)的治疗前景取得了重大进展,包括在羟基脲之后的二线设置中批准了鲁索替尼,聚乙二醇干扰素-α2b,以及一类名为hepcidin模拟物的新型药物的高级临床开发。
■我们对讨论风险分层的证据进行了全面审查,治疗适应症,仅放血方法和关键试验的作用和局限性,涵盖与使用干扰素-α(IFN-α)有关的细微差别,鲁索替尼,铁调素模拟物和即将到来的研究药物,包括HDAC和LSD1抑制剂。
■PV的研究范式正在缓慢地从对血细胞比容控制的唯一关注转向疾病改变。铁调素模拟物的发现是恢复铁稳态的突破,实现静脉切开术的独立性,并可能导致更严格的血细胞比容控制改善无血栓生存率。另一方面,新出现的IFN-α和鲁索替尼以及两种药物的联合使用数据表明,在部分PV患者中实现分子缓解的潜力,等待长期随访,以验证分子反应与无进展和无血栓形成生存期的临床相关结局之间的相关性.
UNASSIGNED: The treatment landscape of polycythemia vera (PV) has seen major advancements within the last decade including approval of ruxolitinib in the second line setting after hydroxyurea, ropegylated interferon-α2b, and advanced clinical development of a novel class of agents called hepcidin mimetics.
UNASSIGNED: We provide a comprehensive review of the evidence discussing the risk stratification, treatment indications, role and limitations of phlebotomy only approach and pivotal trials covering nuances related to the use of interferon-α (IFN-α), ruxolitinib, hepcidin mimetics, and upcoming investigational agents including HDAC and LSD1 inhibitors.
UNASSIGNED: The research paradigm in PV is slowly shifting from the sole focus on hematocrit control and moving toward disease modification. The discovery of hepcidin mimetics has come as a breakthrough in restoring iron homeostasis, achieving phlebotomy-independence and may lead to improved thrombosis-free survival with stricter hematocrit control. On the other hand, emerging data with IFN- α and ruxolitinib as well as combination of the two agents suggests the potential for achieving molecular remission in a subset of PV patients and long-term follow-up is awaited to validate the correlation of molecular responses with clinically relevant outcomes of progression-free and thrombosis-free survival.