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使用常规可得的血液和临床标志物预测对免疫检查点抑制剂的反应和毒性。

Predicting response and toxicity to immune checkpoint inhibitors using routinely available blood and clinical markers.

作者信息

Hopkins Ashley M, Rowland Andrew, Kichenadasse Ganessan, Wiese Michael D, Gurney Howard, McKinnon Ross A, Karapetis Chris S, Sorich Michael J

机构信息

Flinders Centre for Innovation in Cancer, College of Medicine and Public Health, Flinders University, Flinders Drive, Bedford Park, Adelaide, South Australia 5042, Australia.

Department of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Flinders Drive, Bedford Park, Adelaide, South Australia 5042, Australia.

出版信息

Br J Cancer. 2017 Sep 26;117(7):913-920. doi: 10.1038/bjc.2017.274. Epub 2017 Aug 24.

Abstract

Immune checkpoint inhibitors (ICI) are an important development in the treatment of advanced cancer. A substantial proportion of patients treated with ICI do not respond, and additionally patients discontinue treatment due to adverse effects. While many novel biological markers related to the specific mechanisms of ICI actions have been investigated, there has also been considerable research to identify routinely available blood and clinical markers that may predict response to ICI therapy. If validated, these markers have the advantage of being easily integrated into clinical use for nominal expense. Several markers have shown promise, including baseline and post-treatment changes in leucocyte counts, lactate dehydrogenase and C-reactive protein. While promising, the results between studies have been inconsistent due to small sample sizes, follow-up time and variability in the assessed markers. To date, research on routinely available blood and clinical markers has focussed primarily on ICI use in melanoma, the use of ipilimumab and on univariate associations, but preliminary evidence is emerging for other cancer types, other ICIs and for combining markers in multivariable clinical prediction models.

摘要

免疫检查点抑制剂(ICI)是晚期癌症治疗领域的一项重要进展。接受ICI治疗的患者中有很大一部分没有反应,此外,患者还会因不良反应而停止治疗。虽然已经对许多与ICI作用的特定机制相关的新型生物标志物进行了研究,但也有大量研究致力于确定可能预测ICI治疗反应的常规可用血液和临床标志物。如果得到验证,这些标志物具有易于以较低成本整合到临床应用中的优势。几种标志物已显示出前景,包括白细胞计数、乳酸脱氢酶和C反应蛋白的基线及治疗后变化。尽管前景乐观,但由于样本量小、随访时间以及评估标志物的变异性,各研究结果并不一致。迄今为止,关于常规可用血液和临床标志物的研究主要集中在ICI在黑色素瘤中的应用、伊匹单抗的使用以及单变量关联方面,但其他癌症类型、其他ICI以及在多变量临床预测模型中组合标志物的初步证据正在出现。

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