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接受免疫检查点抑制剂治疗的肾细胞癌患者的免疫相关肝脏不良事件:一项回顾性研究。

Immune-related hepatic adverse events in renal cell carcinoma patients treated with immune checkpoint inhibitors: a retrospective study.

作者信息

Saleh Amer, Grünwald Viktor, Hilser Thomas, Darr Christopher

机构信息

University Hospital Essen, Essen, Germany.

出版信息

BJC Rep. 2025 Sep 16;3(1):61. doi: 10.1038/s44276-025-00178-7.

DOI:10.1038/s44276-025-00178-7
PMID:40957947
Abstract

BACKGROUND

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced renal cell carcinoma (RCC), but their use is associated with immune-related adverse events, including hepatic adverse events (irHAEs).

METHODS

We retrospectively analysed 105 RCC patients treated with ICIs as first-line therapy between 2018 and 2023 at the University Hospital of Essen. Patients were categorized by the development of irHAE, defined per CTCAE grading v5.0. Multivariable logistic regression was used to identify risk factors, while Kaplan-Meier survival analyses evaluated PFS and OS.

RESULTS

Among the cohort, 16.19% (n = 17) developed irHAE, while 8.57% (n = 9) experienced higher-grade events. Combination therapy with tyrosine kinase inhibitors (TKIs) was associated with a higher likelihood of irHAE (OR: 7.69, p = 0.037) compared to ICI-only regimens, with cabozantinib showing a significantly shorter time to onset (35 vs. 84 days; p < 0.001). Patients with a BMI ≥ 25 had a significantly increased risk (p = 0.011). Differences in PFS (18.63 vs. 19.87 months; p = 0.099) and OS (27.80 vs. 23.87 months; p = 0.36) were not statistically significant.

CONCLUSIONS

The combination of ICI with TKI posed higher risks for irHAE in RCC patients. While survival outcomes were unaffected, the results underscore the need for tailored monitoring and management. Prospective studies are warranted to refine therapeutic approaches.

摘要

背景

免疫检查点抑制剂(ICIs)彻底改变了晚期肾细胞癌(RCC)的治疗方式,但其使用与免疫相关不良事件有关,包括肝脏不良事件(irHAEs)。

方法

我们回顾性分析了2018年至2023年期间在埃森大学医院接受ICIs一线治疗的105例RCC患者。根据CTCAE v5.0分级定义的irHAE发生情况对患者进行分类。采用多变量逻辑回归确定危险因素,同时进行Kaplan-Meier生存分析评估无进展生存期(PFS)和总生存期(OS)。

结果

在该队列中,16.19%(n = 17)发生了irHAE,而8.57%(n = 9)经历了更高级别的事件。与仅使用ICI的方案相比,酪氨酸激酶抑制剂(TKIs)联合治疗与发生irHAE的可能性更高相关(比值比:7.69,p = 0.037),卡博替尼的起效时间明显更短(35天对84天;p < 0.001)。体重指数(BMI)≥25的患者风险显著增加(p = 0.011)。PFS(18.63个月对19.87个月;p = 0.099)和OS(27.80个月对23.87个月;p = 0.36)的差异无统计学意义。

结论

ICI与TKI联合使用给RCC患者带来了更高的irHAE风险。虽然生存结果未受影响,但结果强调了进行针对性监测和管理的必要性。有必要开展前瞻性研究以优化治疗方法。

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本文引用的文献

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Higher risk of hepatotoxicity associated with cabozantinib in cancer patients.卡博替尼治疗的癌症患者肝毒性风险增加。
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Impact of immunosenescence and inflammaging on the effects of immune checkpoint inhibitors.免疫衰老和炎症衰老对免疫检查点抑制剂疗效的影响。
Cancer Pathog Ther. 2023 Aug 9;2(1):24-30. doi: 10.1016/j.cpt.2023.08.001. eCollection 2024 Jan.
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Immune-Related Adverse Events and Survival Among Patients With Metastatic NSCLC Treated With Immune Checkpoint Inhibitors.免疫检查点抑制剂治疗转移性非小细胞肺癌患者的免疫相关不良反应与生存
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