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免疫检查点抑制剂开始治疗前使用类固醇的时间与黑色素瘤的治疗结果相关吗?一项基于人群的研究。

Is Timing of Steroid Exposure Prior to Immune Checkpoint Inhibitor Initiation Associated with Treatment Outcomes in Melanoma? A Population-Based Study.

作者信息

Nikita Nikita, Banks Joshua, Keith Scott W, Song Andrew, Johnson Jennifer M, Wilson Melissa, Sharma Swapnil, Lu-Yao Grace

机构信息

Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA.

Department of Medical Oncology, Sidney Kimmel Cancer Center (SKCC) at Jefferson, Philadelphia, PA 19107, USA.

出版信息

Cancers (Basel). 2022 Mar 2;14(5):1296. doi: 10.3390/cancers14051296.

Abstract

Immune checkpoint inhibitors (ICIs) harness the immune system and are the therapy of choice for multiple cancers. Although immunosuppressive agents such as steroids are also used in many cancers, it is unknown how their timing affects treatment outcomes. Thus, we investigated the relationship between the timing of steroid exposure preceding ICI administration and subsequent treatment outcomes in melanoma. This population-based study utilized the SEER-Medicare-linked database to identify patients diagnosed with melanoma between 1991 and 2015 and receiving ICIs between 2010 and 2016, examining last steroid exposure in the 12 months preceding ICI. The main outcome was all-cause mortality (ACM) after ICIs. Modifications of the Cox proportional hazards model were used to calculate time-dependent hazards. Of 1671 patients with melanoma receiving ICIs, 907 received steroids. Compared with no steroids, last steroid exposures ≤1 month and 1-3 months prior to ICIs were associated with a 126% and 51% higher ACM within 3 months post ICI initiation, respectively (hazard ratio (HR): 2.26, 95% CI: 1.65-3.08; and HR: 1.51, 95% CI: 1.01-2.27). Steroid exposure within 3 months of initiating ICIs was associated with increased mortality up to 6 months after ICI. Further investigation is warranted to elucidate mechanisms affecting outcomes due to steroids.

摘要

免疫检查点抑制剂(ICIs)可利用免疫系统,是多种癌症的首选治疗方法。尽管类固醇等免疫抑制剂也用于许多癌症治疗,但尚不清楚其使用时机如何影响治疗效果。因此,我们研究了ICI给药前类固醇暴露时机与黑色素瘤后续治疗效果之间的关系。这项基于人群的研究利用SEER - 医疗保险关联数据库,识别1991年至2015年间被诊断为黑色素瘤且在2010年至2016年间接受ICIs治疗的患者,检查ICI前12个月内的最后一次类固醇暴露情况。主要结局是ICI治疗后的全因死亡率(ACM)。使用Cox比例风险模型的修正方法来计算时间依赖性风险。在1671例接受ICIs治疗的黑色素瘤患者中,907例接受了类固醇治疗。与未使用类固醇相比,ICI前最后一次类固醇暴露≤1个月和1 - 3个月时,ICI开始后3个月内的ACM分别高出126%和51%(风险比(HR):2.26,95%置信区间:1.65 - 3.08;HR:1.51,95%置信区间:1.01 - 2.27)。ICI开始后3个月内的类固醇暴露与ICI后长达6个月的死亡率增加相关。有必要进行进一步研究以阐明类固醇影响治疗效果的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bd3/8909505/0ff3bb42507e/cancers-14-01296-g001.jpg

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