Padrnos Leslie, Mesa Ruben A
Oncology (Williston Park). 2017 Jul 15;31(7):521-9.
Despite the identification of JAK mutations and the development of targeted inhibitors, there remain significant unmet needs for patients with myeloproliferative neoplasms. Identification of the myeloproliferative neoplasm populations not currently benefiting from JAK inhibitor therapy highlights the therapeutic deficits still present in this heterogeneous stem cell malignancy. While JAK inhibition has provided significant benefits for patients with intermediate-2 or high-risk myelofibrosis and in patients with polycythemia vera in the second-line setting, JAK inhibitor monotherapy is not approved and not appropriate for all patients with myeloproliferative neoplasms. Continued investigation into additional JAK inhibitors, combination therapy, and novel pathway therapeutics remains key to improving outcomes for all patients with myeloproliferative neoplasms. While therapeutic advances in the JAK inhibitor arena or involving alternative pathways are crucial to improving outcomes in myeloproliferative neoplasms, it is also important to reconsider the role of constitutional symptoms in affected patients as an indication for treatment with agents, such as JAK inhibitors, that can mitigate these debilitating symptoms. In this review, we demonstrate the evolving landscape of clinical investigations that address the important therapeutic needs of patients with myeloproliferative neoplasms.
尽管已鉴定出JAK突变并开发了靶向抑制剂,但骨髓增殖性肿瘤患者仍存在重大未满足需求。确定目前未从JAK抑制剂治疗中获益的骨髓增殖性肿瘤人群,凸显了这种异质性干细胞恶性肿瘤中仍然存在的治疗缺陷。虽然JAK抑制已为中危2或高危骨髓纤维化患者以及二线治疗的真性红细胞增多症患者带来显著益处,但JAK抑制剂单药治疗未获批准,也不适用于所有骨髓增殖性肿瘤患者。继续研究其他JAK抑制剂、联合治疗和新型通路疗法,仍然是改善所有骨髓增殖性肿瘤患者预后的关键。虽然JAK抑制剂领域或涉及替代通路的治疗进展对于改善骨髓增殖性肿瘤的预后至关重要,但重新审视体质性症状在受影响患者中的作用,以此作为使用可减轻这些衰弱症状的药物(如JAK抑制剂)进行治疗的指征也很重要。在本综述中,我们展示了针对骨髓增殖性肿瘤患者重要治疗需求的临床研究的不断演变态势。