Factors associated with liver injury and prognosis in advanced cancer patients treated with immune checkpoint inhibitors.
Factors associated with liver injury and prognosis in advanced cancer patients treated with immune checkpoint inhibitors.
复制标题
与接受免疫检查点抑制剂治疗的晚期癌症患者肝损伤和预后相关的因素。
DOI：
10.1111/hepr.13878
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Okamoto R.
中科院分区：
文献类型：
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作者：
Kaneko S;Asahina Y;Nakagawa M;Murakawa M;Miyazaki Y;Asakage T;Fukuda S;Namiki T;Kano Y;Nagata M;Tsuchiya J;Miyoshi M;Kitahata-Kawai F;Nitta S;Itsui Y;Kakinuma S;Okamoto R.
免疫检查点抑制剂（ICI）的使用显著增加，免疫相关不良事件（irAE）也有所增加。本研究旨在确定与免疫相关性肝损伤（irLI）相关的因素，以及接受ICIs治疗的患者的irLI等级与总生存期（OS）之间的关系。方法回顾性招募了2015年1月至2022年3月期间接受过ICIs治疗的晚期恶性肿瘤患者共571例。通过天冬氨酸转氨酶和丙氨酸转氨酶升高确定是否存在肝损伤。结果50例（8.8%）患者irLI ≥2级，24例（4.2%）患者irLI ≥3级。抗细胞毒性T淋巴细胞相关蛋白-4药物治疗和基线1级天冬氨酸转氨酶/丙氨酸转氨酶升高是≥2级irLI的独立预测因素。抗细胞毒性T淋巴细胞相关蛋白-4治疗是≥3级irLI的唯一独立预测因素。发生任何irAE的患者的中位OS显著长于未发生irAE的患者（风险比0.503，95%CI 0.398- 0.636，p < 0.001）。≥2级irLI患者的中位OS显著延长（HR 0.570，95%CI 0.387- 0.838，p = 0.022）。≥3级irLI患者的中位OS与其他患者之间无显著差异（p= 0.11）。结论抗细胞毒性T淋巴细胞相关蛋白-4药物治疗患者的irLI发生率显著较高。即使在既存1级天冬氨酸转氨酶/丙氨酸转氨酶升高的患者中，适当的随访和irLI控制也可以改善预后。
AimThe use of immune checkpoint inhibitors (ICIs) has increased remarkably, and immune‐related adverse events (irAEs) have also increased. This study aimed to identify factors associated with immune‐related liver injury (irLI), and the relationship between the grades of irLI and overall survival (OS) in patients treated with ICIs.MethodsA total of 571 patients who had been treated for advanced malignancies with ICIs between January 2015 and March 2022 were retrospectively recruited. The presence of liver injury was determined by the aspartate aminotransferase and alanine aminotransferase elevation. The irLI grading was based on Common Terminology Criteria for Adverse Events version 5.0.ResultsA total of 50 (8.8%) patients had grade ≥2 irLI and 24 (4.2%) had grade ≥3 irLI. Treatment with anti‐cytotoxic T‐lymphocyte‐associated protein‐4 agents and baseline grade 1 aspartate aminotransferase/alanine aminotransferase elevation were independent predictive factors of grade ≥2 irLI. Treatment with anti‐cytotoxic T‐lymphocyte‐associated protein‐4 was the only independent predictive factor of grade ≥3 irLI. The median OS for patients who experienced any irAEs was significantly longer than of those without irAEs (hazard ratio 0.503, 95% CI 0.398–0.636,p< 0.001). The median OS in patients with grade ≥2 irLI was significantly longer (HR 0.570, 95% CI 0.387–0.838,p= 0.022). There was no significant difference between the median OS in patients with grade ≥3 irLI and the others (p= 0.11).ConclusionThe incidence of irLI was significantly higher in patients treated with anti‐cytotoxic T‐lymphocyte‐associated protein‐4 agents. Even in patients with pre‐existing grade 1 aspartate aminotransferase/alanine aminotransferase elevation, appropriate follow‐up and control of the irLI can improve the prognosis.