Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Expert Rev Hematol. 2021 Aug;14(8):687-696. doi: 10.1080/17474086.2021.1959315. Epub 2021 Aug 6.
Systemic mastocytosis (SM) is a rare myeloid neoplasm driven in ≈95% of cases by activating mutations, usually D816V. SM can be indolent (ISM), smoldering (SSM) and advanced (AdvSM), the latter characterized by organ damage resulting from infiltrating neoplastic mast cells. The vast majority of cases are indolent, with near-normal life expectancy, although symptoms can be severe. AdvSM, comprising aggressive SM, SM with an associated hematologic neoplasm and mast cell leukemia, however, carries a poor prognosis. Avapritinib is a highly potent and selective inhibitor of mutant .
We provide an overview of SM, including the current therapeutic landscape, and discuss avapritinib in detail: its chemistry and discovery, pharmacodynamic and pharmacokinetic data, current approval status and safety and efficacy profiles in both advanced and non-advanced SM.
With a response rate of 75% amongst evaluable patients with AdvSM and marked reductions observed in measures of mast cell and disease burden, avapritinib stands out as a highly effective targeted therapy for this mutant -driven disease. Cognitive impairment may occur, and intracranial hemorrhage has been reported, particularly in association with severe thrombocytopenia. Early results in patients with ISM/SSM are encouraging. Avapritinib is now approved in the US for AdvSM.
全身性肥大细胞增多症（SM）是一种罕见的髓系肿瘤，约 95%的病例由激活突变驱动，通常为 D816V。SM 可以是惰性的（ISM）、冒烟型（SSM）和进展性的（AdvSM），后者的特征是浸润性肿瘤肥大细胞导致的器官损伤。绝大多数病例是惰性的，预期寿命接近正常，尽管症状可能很严重。然而，进展性 SM、伴有相关血液肿瘤的 SM 和肥大细胞白血病构成了不良预后。Avapritinib 是一种高度有效和选择性的突变体抑制剂。
我们提供了对 SM 的概述，包括当前的治疗现状，并详细讨论了 avapritinib：它的化学和发现、药效学和药代动力学数据、在 AdvSM 和非 AdvSM 中的当前批准状态以及安全性和疗效概况。
在可评估的 AdvSM 患者中，avapritinib 的反应率为 75%，并且观察到肥大细胞和疾病负担的显著减少，这使其成为这种突变驱动疾病的一种非常有效的靶向治疗方法。可能会发生认知障碍，并且已经报道了颅内出血，特别是与严重血小板减少症相关的出血。在 ISM/SSM 患者中的早期结果令人鼓舞。avapritinib 现已在美国获批用于 AdvSM。
