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接受检查点抑制剂治疗的癌症患者并发感染会显著增加免疫相关不良事件的风险。

Co-Occurring Infections in Cancer Patients Treated with Checkpoint Inhibitors Significantly Increase the Risk of Immune-Related Adverse Events.

作者信息

Grabska Siranuysh, Grabski Hovakim, Makunts Tigran, Abagyan Ruben

机构信息

Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA.

L.A. Orbeli Institute of Physiology, National Academy of Sciences, Yerevan 0028, Armenia.

出版信息

Cancers (Basel). 2024 Aug 11;16(16):2820. doi: 10.3390/cancers16162820.

Abstract

Therapeutic antibodies designed to target three immune checkpoint proteins have been applied in the treatment of various malignancies, including small and non-small cell lung cancers, melanoma, renal cell carcinoma, and others. These treatments combat cancers by reactivating cytotoxic T cells. Nevertheless, this mode of action was found to be associated with a broad range of immune-related adverse events (irAEs), including pneumonitis, sarcoidosis, myocarditis, nephritis, colitis, and hepatitis. Depending on their severity, these irAEs often necessitate the suspension or discontinuation of treatment and, in rare instances, may lead to fatalities. We analyzed over nineteen million reports and identified over eighty thousand adverse event reports from patients treated with immune checkpoint inhibitors submitted to the Food and Drug Administration's Adverse Event Reporting System MedWatch. Reports concerning pembrolizumab, nivolumab, cemiplimab, avelumab, durvalumab, atezolizumab, and ipilimumab revealed a statistically significant association between the irAEs and concurrent infectious diseases for five out of seven treatments. Furthermore, the association trend was preserved across all three types of checkpoint inhibitors and each of the five individual therapeutic agent cohorts, while the remaining two showed the same trend, but an increased confidence interval, due to an insufficient number of records.

摘要

旨在靶向三种免疫检查点蛋白的治疗性抗体已应用于各种恶性肿瘤的治疗,包括小细胞肺癌和非小细胞肺癌、黑色素瘤、肾细胞癌等。这些治疗方法通过重新激活细胞毒性T细胞来对抗癌症。然而,人们发现这种作用方式与广泛的免疫相关不良事件(irAE)有关,包括肺炎、结节病、心肌炎、肾炎、结肠炎和肝炎。根据其严重程度,这些irAE通常需要暂停或停止治疗,在极少数情况下,可能会导致死亡。我们分析了超过1900万份报告,并从提交给美国食品药品监督管理局不良事件报告系统MedWatch的接受免疫检查点抑制剂治疗的患者中识别出8万多份不良事件报告。关于帕博利珠单抗、纳武利尤单抗、西米普利单抗、阿维鲁单抗、度伐利尤单抗、阿替利珠单抗和伊匹木单抗的报告显示,在七种治疗中的五种治疗中,irAE与并发传染病之间存在统计学上的显著关联。此外,在所有三种类型的检查点抑制剂以及五个单独治疗药物队列中的每一个队列中,这种关联趋势都得以保留,而其余两个队列显示出相同的趋势,但由于记录数量不足,置信区间有所增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7adc/11352782/be500867dc2b/cancers-16-02820-g0A1.jpg

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