阿金尼布Asciminib

Asciminib potently inhibits ABL1 kinase activity of the BCR-ABL1 fusion protein via allosteric binding to the ABL myristoyl pocket; it is a STAMP (Specifically Targeting the ABL Myristoyl Pocket) inhibitor. Asciminib demonstrated activity against wild-type BCR-ABL1 and several mutant forms. 

Indications and doses: 1. chronic myeloid leukemia, Ph+, chronic phase, previously treated with ≥2 tyrosine kinase inhibitors: Oral: 80 mg once daily or 40 mg twice daily; 2. chronic myeloid leukemia, Ph+, chronic phase, with T315I mutation: Oral: 200 mg twice daily (two dosing plans are very different, which healthcare providers should be alerted for ).

Toxicity monitoring includes CBC every 2 weeks for the first 3 months and monthly thereafter or as clinically necessary; serum lipase and amylase levels monthly or as clinically necessary;  • Bone marrow suppression: Thrombocytopenia, neutropenia, and anemia have occurred with asciminib, including grade 3 and 4 events.  • Cardiovascular toxicity: Cardiovascular toxicity, including ischemic cardiac and CNS conditions, arterial thrombotic and embolic conditions, and heart failure, has been reported. Grade 3 and 4 cardiovascular toxicity has occurred.

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阿金尼布Asciminib通过与BCR-ABL肉豆蔻口袋的别构性结合，有力地抑制了BCR-ABL1融合蛋白的ABL1激酶活性；另外它是一种STAMP（专门针对ABL肉豆蔻口袋; Specifically Targeting the ABL Myristoyl Pocket）抑制剂。阿金尼布Asciminib对野生型BCR-ABL1和几种突变型显示出活性。

- 适应症和剂量:  1, 慢性Ph+骨髓性白血病的慢性期，≥2种酪氨酸激酶抑制剂治疗后疾病进展:  口服80毫克每日一次，或40毫克每日两次。2, 慢性Ph+骨髓性白血病的慢性期，T315I突变型：200毫克每日两次（两种给药方案的剂量有很大的不同，需要医疗服务机构提高警惕, 以防医疗错误发生）。

- 毒性监测: 治疗前3个月每2周一次的CBC，随后每月一次(或根据临床需要)；每月一次血清脂肪酶和淀粉酶水平(或根据临床需要)。 - 骨髓抑制: 血小板减少、中性粒细胞减少和贫血，包括3级和4级事件。- 心血管毒性: 已有心血管毒性的报告，包括缺血性心脏和中枢神经系统状况，动脉血栓和栓塞状况，以及心力衰竭。发生过3级和4级的心血管毒性。