Retrospective analysis of clinical trial safety data for pembrolizumab reveals the effect of co-occurring infections on immune-related adverse events.
Retrospective analysis of clinical trial safety data for pembrolizumab reveals the effect of co-occurring infections on immune-related adverse events.
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对pembrolizumab的临床试验安全数据的回顾性分析揭示了同时发生感染对免疫相关不良事件的影响。
DOI：
10.1371/journal.pone.0263402
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
Lee P
中科院分区：
文献类型：
--
作者：
Makunts T;Burkhart K;Abagyan R;Lee P
靶向PD-1、PD-L1和CTLA-4免疫检查点蛋白的生物制剂已被用于多种肿瘤类型，包括小细胞和非小细胞肺癌、黑色素瘤和肾细胞癌。它们的抗肿瘤活性是通过放大患者自身免疫系统的成分来靶向逃避癌细胞的免疫反应来实现的。然而，这种独特的作用机制会引起一系列与免疫相关的不良事件，即影响体内多个生理系统的irae。根据严重程度，这些irae通常导致暂停或停止治疗，在极少数情况下，可能导致致命的结果。在这项研究中，我们专注于pembrolizumab，一种PD-1抑制剂，目前被批准用于多种类型的癌症。我们分析了来自Keynote临床试验的一万多份不良事件报告，这些报告来自派姆单抗治疗各种癌症适应症，伴有或不伴有共发感染，并观察到感染受试者发生irAE的风险在统计学上显著增加80%。
Biologics targeting PD-1, PD-L1, and CTLA-4 immune checkpoint proteins have been used in a variety of tumor types including small and non-small cell lung cancers, melanoma, and renal cell carcinoma. Their anti-tumor activity is achieved through amplifying components of the patient’s own immune system to target immune response evading cancer cells. However, this unique mechanism of action causes a range of immune related adverse events, irAEs, that affect multiple physiological systems in the body. These irAEs, depending on severity, often cause suspension or discontinuation of therapy and, in rare cases, may lead to fatal outcomes. In this study we focused on pembrolizumab, a PD-1 inhibitor currently approved for multiple types of cancer. We analyzed over ten thousand adverse event reports from Keynote clinical trials of pembrolizumab for various cancer indications with or without co-occurring infections, and observed a statistically significant 80% increase in the risk of developing an irAE in subjects with infections.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
--
作者：
Lee, AN;Werth, VP
通讯作者：
Werth, VP
DOI：
10.1016/j.berh.2004.05.006
发表时间：
2004-10-01
影响因子：
5.2
作者：
Olsen, NJ
通讯作者：
Olsen, NJ
影响因子：
4.2
作者：
Brown, EG;Wood, L;Wood, S
通讯作者：
Wood, S
影响因子：
3.5
作者：
Molina, V;Shoenfeld, Y
通讯作者：
Shoenfeld, Y