不确定潜能克隆造血(CHIP)及其与实体肿瘤患者治疗结果和不良事件的关联

IF 2 Q3 ONCOLOGY
Tharani Krishnan, Joao Paulo Solar Vasconcelos, Emma Titmuss, Robert J Vanner, David F Schaeffer, Aly Karsan, Howard Lim, Cheryl Ho, Sharlene Gill, Stephen Yip, Stephen K Chia, Hagen F Kennecke, Derek J Jonker, Eric X Chen, Daniel J Renouf, Chris J O'Callaghan, Jonathan M Loree
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摘要

不确定电位克隆造血(CHIP)是从体细胞突变中克隆扩增的造血干细胞。它是在无细胞DNA (cfDNA)中常见的偶然发现。我们调查了实体肿瘤患者cfDNA中CHIP的发生率,并探讨了其与治疗结果和不良事件的关系。我们回顾了当地前瞻性实体肿瘤队列(predict - 1)和两项随机试验的cfDNA结果:CCTG CO.26(转移性结直肠癌的durvalumab + tremelimumab [D+T]或最佳支持治疗)和CCTG PA.7(转移性胰腺腺癌的吉西他滨和nab-紫杉醇+/- D+T)。CHIP+被定义为DNMT3A、TET2或ASXL1中变异等位基因频率(VAF)≥2%的任何突变,假定的种系变异(VAF bb0 40%)被去除。评价cfDNA治疗后一线治疗的3级毒性和剂量限制性毒性。在纳入的465例患者中,CHIP的患病率为10-30%,并且随着年龄的增长更为常见(p=0.003)。DNMT3A是所有队列中最常发生突变的基因。与CHIP治疗相比,接受免疫治疗的PA.7 CHIP患者的无进展生存期(PFS)有所改善(HR 0.55 [0.28-1.07], p=0.079, p-相互作用=0.098[多变量])。然而,在predict - 1中,CHIP患者接受化疗后,PFS呈恶化趋势(HR 1.82 [0.98-3.38], p=0.059)。接受化疗或免疫治疗的CHIP+/-组之间的不良事件发生率无差异。CHIP常见于实体肿瘤患者。尽管CHIP似乎不会影响不良事件的发生率,但它可能会影响免疫治疗或化疗的结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clonal Hematopoiesis of Indeterminate Potential and its Association with Treatment Outcomes and Adverse Events in Patients with Solid Tumors.

Significance: Liquid biopsy is increasingly being used in oncology for tumor molecular characterization. CHIP is a common incidental finding in cfDNA, and its prevalence increases with age. This study builds on growing evidence of common CHIP variants in patients with solid tumors. The results suggest a possible clinical impact of CHIP on treatment outcomes from immunotherapy or chemotherapy. This may have implications for treatment selection for patients with solid tumors.

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