Knight Cancer Institute.
Division of Hematology & Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, Oregon, USA.
Curr Opin Hematol. 2019 Mar;26(2):112-118. doi: 10.1097/MOH.0000000000000486.
The purpose of this review is to summarize the pathophysiology of systemic mastocytosis, review the most recent clinical trials and drug development in systemic mastocytosis, with a specific focus on the advanced systemic mastocytosis subtypes.
Systemic mastocytosis is a clonal neoplasm of mast cells that has had a number of successful therapeutic options being developed in the past few years. The first therapeutic agent to be Food and Drug Administration (FDA) approved in decades was midostaurin in 2017 with a 60% response rate % with improvement in both end-organ damage and symptoms. However, complete responses/remissions with midostaurin have been elusive. Additional clinical trials of tyrosine kinase inhibitors that target the proto-oncogene receptor tyrosine kinase (KIT) mutation show great promise. The two drugs with promising early clinical trial data include avapritinib and DCC-2618 with avapritinib showing potential to induce complete remissions.
Therapies for systemic mastocytosis are in a stage of evolution with further elucidation of additional mutations associated with oncogenesis in addition to the most commonly described KIT (give details), ongoing clinical trials could potentially with lead to further targeted therapy and increased complete responses and durable remissions.
本文旨在总结系统性肥大细胞增多症的病理生理学，综述系统性肥大细胞增多症最新的临床试验和药物研发进展，重点关注晚期系统性肥大细胞增多症亚型。
近年来，系统性肥大细胞增多症已出现多种治疗选择，并取得了一定的成效。2017 年，米哚妥林成为几十年来首个获得美国食品药品监督管理局（FDA）批准的治疗药物，应答率达 60%，可改善终末器官损伤和症状。然而，米哚妥林并不能完全缓解病情。靶向原癌基因受体酪氨酸激酶（KIT）突变的酪氨酸激酶抑制剂的临床试验也取得了良好的效果。两项具有良好早期临床试验数据的药物包括 avapritinib 和 DCC-2618，avapritinib 有诱导完全缓解的潜力。
系统性肥大细胞增多症的治疗方法正在不断发展，除了最常见的 KIT 突变外，还进一步阐明了与肿瘤发生相关的其他突变。随着更多临床试验的开展，可能会出现更多针对特定靶点的治疗方法，从而提高完全缓解率和持久缓解率。
