对复发性/耐药性慢性淋巴细胞白血病的响应适应的,时间有限的venetoclax,umbralisib和ublituximab
Brian T Hill1, Shuo Ma2, Clive S Zent3
1Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
Blood advances
|October 23, 2023
概括
使用venetoclax和U2 (umbralisib和ublituximab) 的新型组合疗法在治疗复发性/耐药性慢性淋巴细胞白血病 (CLL) 中显示出高疗效,包括对布鲁顿氨酸激酶 (BTK) 抑制剂耐药的治疗.
科学领域:
- 血液学 血液学 血液学
- 在瘤学瘤学.
- 临床试验 临床试验
背景情况:
- 慢性淋巴细胞白血病 (CLL) 通常会对布鲁顿氨酸激酶 (BTK) 抑制剂产生耐药性.
- 酸丁醇-3-酶 (PI3K) 抑制剂,如乌布拉利西布在复发性/耐药性CLL中表现出活性,但具有毒性风险.
- 联合PI3K和BCL-2抑制提供了协同作用的抗瘤效应.
研究的目的:
- 评估一个适应应答的,时间有限的疗法的安全性和有效性,该疗法结合了venetoclax,umbralisib和ublituximab (U2-VeN).
- 为了优化疾病控制,同时最大限度地减少长期治疗毒性复发性/耐药性CLL和里希特转换.
- 在CLL患者中停止治疗后评估不可检测的最小残留疾病 (uMRD) 率.
主要方法:
- 一个1/2期临床试验,涉及46名复发性/耐药性CLL患者和5名里希特转换患者.
- 治疗包括venetoclax,umbralisib和ublituximab (U2-VeN) 在最多12个周期内进行.
- 对于CLL患者来说,停止治疗,以达到不可检测的最小残留疾病 (uMRD).
主要成果:
- 对CLL的总体应答率为98% (42%的完整反应).
- 在治疗结束时,骨髓的MURD率为77% (在10^-4),其中71%的患者在之前的BTK抑制剂中耐药.
- 关键不良事件包括腹 (50%) 和肝酶升高 (33%);随着门诊venetoclax的启动,没有发生瘤溶解综合征.
结论:
- 时间有限的venetoclax和U2联合治疗对于复发性/耐药性CLL是安全且非常有效的.
- 这种方法在以前用共价BTK抑制剂治疗的患者中特别有效.
- 响应适应的,时间有限的治疗可以优化结果,并减轻CLL管理中的毒性.
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