卡度尼利单抗相关肝损伤的发生规律及临床特征分析

Analysis of the occurrence pattern and clinical characteristics of liver injury related to cadonilimab

摘要

目的: 分析卡度尼利单抗相关肝损伤的发生规律及临床特点,为患者制定个体化用药方案提供参考。方法: 收集2021年1月—2023年12月期间,在湖南省肿瘤医院接受卡度尼利单抗治疗并出现肝损伤的肿瘤患者病例资料,详细记录患者个人信息、疾病信息、用药信息、肝损伤情况以及不良反应处置转归等信息。结果: 共纳入14例患者,男性11例、女性3例,中位年龄57岁,原发疾病以肺癌患者为主(57.14%)。从用药情况来看,64.28%的患者按照药品说明书推荐的用法用量,而35.72%的患者存在超说明书用药的情况。11例患者存在联合用药,安罗替尼联合治疗方案占比最高(45.45%),其次为仑伐替尼(18.18%)。卡度尼利单抗相关肝损伤的中位发生时间为65 d,71.43%的患者发生于用药后3个月内,3级及以上肝损伤占比60.00%。从肝损伤的类型来看,多数患者(71.42%)表现为肝细胞损伤型,其中谷丙转氨酶(alanine aminotransferase,ALT)和谷草转氨酶(aspartate aminotransferase,AST)的中位数值分别达到了324.0和430.9 U·L^－1。临床表现以乏力(21.43%)、黄疸(7.14%)为主,71.43%的患者经激素及护肝治疗后好转,28.57%的患者需长期随访监测肝功能。结论: 卡度尼利单抗相关肝损伤多发生于用药早期,以肝细胞损伤型为主,3级及以上肝损伤占比较高。联合用药(如安罗替尼、铂类)可能增加肝损伤风险。建议治疗初期应加强肝功能监测,对症处理后可明显改善预后。

Abstract

Objective: To analyze the occurrence pattern and clinical characteristics of liver injury related to cadonilimab, and provide a reference for formulating individualized medication regimens for patients. Methods: The medical data of cancer patients who received cadonilimab treatment and developed liver injury in Hunan Cancer Hospital from January 2021 to December 2023 were collected. Information such as patients' personal information, disease information, medication information, liver injury status, and the outcomes of adverse reaction management were recorded in detail. Results: A total of 14 patients were included, with 11 males and 3 females, and the median age was 57 years. The primary disease was mainly lung cancer (57.14%). In terms of medication, 64.28% of the patients used cadonilimab according to the recommended dosage and administration method in the instruction manual, while 35.72% of the patients had off-label medication. A total of 11 patients were treated with combination therapy, and anlotinib combination therapy accounted for the highest proportion (45.45%), followed by lenvatinib (18.18%). The median occurrence time of cadonilimab-related liver injury was 65 days, and 71.43% of the patients developed it within 3 months after medication. Liver injury of grade 3 and above accounted for 60.00%. In terms of the type of liver injury, most patients (71.42%) showed hepatocellular injury type, and the median values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) reached 324.0 U·L^－1 and 430.9 U·L^－1 respectively. The clinical manifestations were mainly fatigue (21.43%) and jaundice (7.14%). 71.43% of the patients improved after hormone and liver protection treatment, and 28.57% needed long-term follow-up and monitoring of liver function. Conclusion: Cadonilimab-related liver injury mostly occurs in the early stage of medication, mainly in the form of hepatocellular injury, and the proportion of liver injury of grade 3 and above is relatively high. Combined medication (such as anlotinib) may increase the risk of liver injury. It is recommended to strengthen the monitoring of liver function in the initial stage of treatment, and the prognosis can be significantly improved after symptomatic treatment.

关键词

卡度尼利单抗 / 肝损伤 / 不良反应 / 发生规律 / 临床特征分析

Key words

cadonilimab / liver injury / adverse drug reaction / incidence pattern / analysis of clinical characteristics

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基金资助

中国博士后科学基金资助项目(2023M732333);烟台市科技局资助项目(2023YD064);滨州医学院中医药学科融合科技计划专项资助项目(2024ZYYKJ11);西藏自治区自然基金资助项目(XZ202501ZR0109)