Co-occurring infections in cancer patients treated with checkpoint inhibitors significantly increase the risk of immune related adverse events.
Co-occurring infections in cancer patients treated with checkpoint inhibitors significantly increase the risk of immune related adverse events.
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使用检查点抑制剂治疗的癌症患者并发感染会显着增加免疫相关不良事件的风险。
DOI：
10.1101/2024.02.14.24302840
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Abagyan,Ruben
中科院分区：
文献类型：
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作者：
Makunts,Tigran;Grabska,Siranuysh;Grabski,Hovakim;Abagyan,Ruben
针对PD-1、PD-L1和CTLA-4等免疫检查点蛋白设计的治疗性抗体已被应用于各种肿瘤类型的治疗，包括小细胞和非小细胞肺癌、黑色素瘤、肾细胞癌等。这些治疗方法通过重新激活CD8细胞毒性T细胞来对抗癌症。然而，这种独特的靶向作用模式被发现与更广泛的免疫相关不良事件相关，irAEs影响多个生理系统。根据其严重程度，这些irAEs往往需要暂停或停止治疗，在极少数情况下，可能会导致致命的后果。在这项研究中，我们调查了接受PD-1、PD-L1和CTLA-4抑制剂治疗的患者中超过8万例irAEs的不良事件报告。使用FDA不良事件报告系统MedWatch提交的数据作为数据来源。这些治疗药物包括pembrolizumab、nivolumab、cymplimab、avelumab、duvalumab、atezolizumab和ipilimumab。对这些报告的数据分析显示，与免疫相关的不良事件，包括在治疗期间经历传染病的患者发生的严重和危及生命的事件，在统计上具有显著的相关性。此外，在所有三类检查点抑制剂和七个单独的治疗剂队列中的每一个中，这种关联趋势都得到了保留。
Therapeutic antibodies designed to target immune checkpoint proteins such as PD-1, PD-L1, and CTLA-4 have been applied in the treatment of various tumor types, including small and non-small cell lung cancers, melanoma, renal cell carcinoma, and others. These treatments combat cancers by reactivating CD8 cytotoxic T-cells. Nevertheless, this unique targeted mode of action was found to be associated with a broader range of immune-related adverse events, irAEs, affecting multiple physiological systems. Depending on their severity, these irAEs often necessitate the suspension or discontinuation of treatment and, in rare instances, may lead to fatal consequences. In this study we investigated over eighty thousand adverse event reports of irAEs in patients treated with PD-1, PD-L1, and CTLA-4 inhibitors. FDA Adverse Event Reporting System MedWatch submissions were used as the data source. These therapeutics included pembrolizumab, nivolumab, cemiplimab, avelumab, durvalumab, atezolizumab, and ipilimumab. The data analysis of these reports revealed a statistically significant association of immune related adverse events, including serious and life-threatening events in patients who experienced infectious disease during treatment. Additionally, the association trend was preserved across all the three classes of checkpoint inhibitors and each of the seven individual therapeutic agent cohorts.