在先前接受过acalabrutinib或ibrutinib治疗的慢性淋巴细胞白血病进展患者的突变特征
Jennifer A Woyach1, Daniel Jones1,2, Wojciech Jurczak3
1The Ohio State University Comprehensive Cancer Center, Columbus, OH.
Blood
|May 16, 2024
概括
慢性淋巴细胞白血病 (CLL) 中的布鲁顿氨酸激酶 (BTK) 抑制剂耐药性涉及新兴突变. 阿卡拉布鲁丁尼和易布鲁丁尼显示出不同的BTK突变模式,包括阿卡拉布鲁丁尼的新型变异.
科学领域:
- 在瘤学瘤学.
- 血液学 血液学 血液学
- 遗传学 遗传学 是一个
背景情况:
- 在布鲁顿氨酸激酶 (BTK) 抑制剂治疗下慢性淋巴细胞白血病 (CLL) 的进展通常与B细胞受体通路中的获得突变有关.
- 了解这些突变对于管理复发性/耐药性CLL至关重要.
研究的目的:
- 分析复发性/耐药性CLL在acalabrutinib或ibrutinib治疗中进展的患者的克隆进化和突变模式.
- 为了比较两个治疗组之间的新出现的布鲁顿氨酸激酶 (BTK) 和其他途径突变.
主要方法:
- 来自ELEVATE-RR试验患者的对对外周围血液样本 (基线和进展) 的分析.
- 下一代测序用于识别BTK,TP53和PLCG2.2中的新兴突变.
- 在acalabrutinib和ibrutinib组之间比较突变频率,变异性等位基因分数 (VAF) 和特定突变类型.
主要成果:
- 新出现的BTK突变发生在66%的acalabrutinib治疗患者和37%的ibrutinib治疗患者中. 在两者中BTK C481S是常见的;acalabrutinib显示出独特的T474I和E41V突变.
- 在13% (acalabrutinib) 和7% (ibrutinib) 的患者中观察到新出现的TP53突变,具有明显的中位数VAFs.
- 新出现的PLCG2突变在ibrutinib (20%) 时比acalabrutinib (6%) 更频繁,具有不同的BTK/PLCG2转换模式.
结论:
- 虽然BTK C481突变在两种药物中都是常见的,但acalabrutinib和ibrutinib在CLL进展中表现出不同的突变和突变模式.
- 新型BTK变异如T474I和E41V与acalabrutinib相关,而L528W和A428D与ibrutinib相关.
- 这些发现突出了不同BTK抑制剂下的不同克隆进化机制,影响了复发性/耐药性CLL的治疗策略.
相关概念视频
02:07Tumor Progression
6.3K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.3K
02:50Combination Therapies and Personalized Medicine
4.9K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.9K