Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
Department of Hematology, University Medical Center, University of Groningen, Groningen, The Netherlands.
Expert Opin Biol Ther. 2021 Apr;21(4):487-498. doi: 10.1080/14712598.2021.1837109. Epub 2021 Jan 15.
Systemic mastocytosis (SM) is characterized by the overproduction and accumulation of neoplastic mast cells (MCs) in the bone marrow, skin, and visceral organs. The D816V mutation is found in approximately 90% of cases. In advanced SM (advSM), inferior survival often relates to MC-induced organ damage that may impact multiple organ systems. In addition, mediator symptoms related to MC activation can severely impact the quality of life. The oral multikinase/KIT inhibitor midostaurin was approved by the US Food and Drug Administration and the European Medicines Agency as monotherapy for advSM based on data from phase 2 clinical studies.
This review discusses the management of common adverse events (AEs) in patients with advSM who participated in phase 2 clinical studies that led to the approval of midostaurin.
In the advSM population undergoing treatment with midostaurin, treatment-related AEs are often difficult to distinguish from disease-related symptoms, which can lead to premature discontinuation and improper dose reduction of midostaurin therapy in patients who might have benefitted from continued therapy. Here we present strategies to help optimize AE management and maximize the potential benefits of midostaurin in advSM.
系统性肥大细胞增多症（SM）的特征是骨髓、皮肤和内脏器官中恶性肥大细胞（MC）的过度产生和积累。大约 90%的病例存在 D816V 突变。在晚期 SM（advSM）中，较差的生存率通常与 MC 诱导的器官损伤有关，这可能影响多个器官系统。此外，与 MC 激活相关的介质症状会严重影响生活质量。口服多激酶/KIT 抑制剂米哚妥林基于 2 期临床研究的数据被美国食品和药物管理局（FDA）和欧洲药品管理局（EMA）批准用于 advSM 的单药治疗。
本文讨论了在参与导致米哚妥林获批的 2 期临床研究的 advSM 患者中，管理常见不良反应（AE）的方法。
在接受米哚妥林治疗的 advSM 人群中，治疗相关 AE 通常难以与疾病相关症状区分，这可能导致过早停止和不适当减少米哚妥林治疗剂量，而这些患者可能从继续治疗中受益。在此，我们提出了优化 AE 管理的策略，以最大限度地发挥米哚妥林在 advSM 中的潜在益处。
