亚西明尼布加达沙替尼布和普雷尼松治疗费城染色体阳性急性白血病
Marlise R Luskin1, Mark A Murakami1, Julia Keating2
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Blood
|October 7, 2024
概括
结合达沙提尼布和阿西米尼布,为费城染色体阳性急性淋巴细胞白血病 (Ph+ ALL) 提供安全有效的治疗方法,显示出深度反应并防止耐药性. 这种组合疗法在1期临床试验中显示出高缓解率.
科学领域:
- 血液学 血液学 血液学
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 达沙替尼对费城染色体阳性 (Ph+) 白血病有效,但可能会产生耐药性.
- 阿西米尼布是一种BCR::ABL1的全抑制剂,为组合疗法提供了一种新的机制.
- 结合疗法可能会加深 Ph+ ALL 患者的反应并克服耐药性.
研究的目的:
- 为了确定阿斯基米尼布与达沙替尼布和普雷德尼松联合使用的最大耐受剂量 (MTD).
- 评估双重BCR::ABL1抑制在Ph+ALL中的安全性和有效性.
- 为了确定阿西米尼布在这种组合中推的第二阶段剂量 (RP2D).
主要方法:
- 一期临床试验 (NCT03595017) 涉及24名患有Ph+ALL或在淋巴细胞爆发危机中的慢性髓性白血病的成年人.
- 阿西米尼布与达沙替尼布 (每日140毫克) 和普雷迪尼松 (每日60毫克/平方米) 结合的每日剂量升级.
- 剂量升级以确定MTD,然后评估血液学,细胞遗传学和分子缓解率.
主要成果:
- 建议的第2期阿斯基米尼布剂量为每天80毫克.
- 剂量限制性毒性是每天160毫克的无症状3级胰腺酶升高.
- 观察到完全血液学缓解的高率 (100%到第84天) 和完全细胞遗传缓解 (100%到第84天).
- 到第84天,89%的患者获得了可测量的残留疾病负面影响.
结论:
- 用达沙替尼布和阿西米尼布抑制双重BCR::ABL1是安全的,并且在新的Ph+ALL中表现出令人鼓舞的活性.
- 组合疗法加深了反应,并可能防止抗达沙替尼布克隆的出现.
- 这种方法需要在更大的临床试验中对Ph + ALL进行进一步的研究.
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