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免疫检查点抑制剂停止免疫相关不良事件的生殖线预测
Pooja Middha1, Rohit Thummalapalli2, Zoe Quandt3,4
1Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
medRxiv : the preprint server for health sciences
|July 1, 2024
概括
自身免疫性疾病的多基因风险得分较高与由于免疫相关不良事件 (irAEs) 导致免疫检查点抑制剂 (ICI) 的早期中止有关. 这种遗传风险可能有助于对ICI治疗的患者进行分层,特别是那些接受组合治疗的患者.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
背景情况:
- 免疫检查点抑制剂 (ICI) 对固体瘤有效,但可能导致与免疫相关的不良事件 (irAEs).
- 预测严重的IRE需要ICI停止仍然具有挑战性.
- 生殖系遗传因素可能会影响irAE的发展和治疗结果.
研究的目的:
- 在肺癌患者中调查自身免疫性疾病 (PRS_AD) 的生殖线多基因风险评分和由于irAEs而停止ICI之间的关联.
- 探索PRS_AD是否可以预测ICI治疗的早期停止.
- 评估PRS_AD对接受ICI组合治疗的患者的IRAE的影响.
主要方法:
- 分析了一组1,327名接受ICI治疗的肺癌患者 (2009-2022年).
- 考克斯的比例危险模型评估了PRS_AD和ICI因IRAE停止之间的关联.
- 分层后勤回归分析了根据治疗类型和疾病阶段的差异效应.
主要成果:
- 增加的PRS_AD与由于iraes的ICI停止有关 (HR每SD=1.18,P=0.03).
- 这种关联在三个月内早期戒烟时更为强烈 (HR/SD=1.38,P=0.01).
- 在PRS_AD百分位上位的患者有更高的早期停药率 (7.2%对3.9%).
- 组合ICI治疗显示出更强的关联 (OR/SD=1.86,P=0.04).
结论:
- 由PRS_AD表示的生殖系遗传倾向与由于irAEs的早期ICI中止有关.
- 在ICI临床决策中,PRS_AD可以作为风险分层的辅助工具.
- 这些发现突显了生殖系遗传学在预测irAEs和指导固体瘤治疗策略方面的作用.
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