目的 研究恶性肿瘤患者应用替雷利珠单抗的血药浓度与发生免疫相关不良事件(irAEs)的相关性,并分析影响血药浓度的因素.方法 选择用替雷利珠单抗治疗的恶性肿瘤患者为研究对象,用液相色谱-串联质谱法检测其血药浓度.观察患者治疗期间irAEs的发生情况,并分析血药浓度与irAEs之间的相关性.同时,收集患者的诊疗资料,分析其对血药浓度的影响.结果 纳入分析的50例接受替雷利珠单抗治疗的恶性肿瘤患者中,共有34例发生了 irAEs,发生率为68％,包括甲状腺功能减退、皮疹、肝功能功损害等.发生irAEs组患者的平均血药浓度为16.69 μg·mL-1显著高于未发生irAEs组的8.41μg·mL-1,在统计学上差异有统计学意义(P＜0.05).其中,发生甲状腺功能减退患者的平均血药浓度为20.98 µg·mL-1显著高于未发生组的11.04 µg·mL-1,发生肝功能损伤患者的平均血药浓度为23.47 μg·mL-1显著高于未发生组的12.06μg·mL-1,在统计学上差异均有统计学意义(均P＜0.05),相关风险的阈值浓度分别为14.61和13.19μg·mL-1.同时通过分析患者临床特征,结果显示,联合化疗组患者的平均血药浓度为9.67 μg·mL-1显著低于未联合组的19.03μg·mL-1,非小细胞肺癌组患者的血药浓度为12.74 μg·mL-1显著低于其他组的20.31 μg·mL-1,在统计学上差异均有统计学意义(均P＜0.05).结论 较高的替雷利珠单抗血药浓度会增加患者发生甲状腺功能减退和肝功能损伤的风险.
Objective To investigate the correlation between blood concentration of tislelizumab and immune-related adverse events(irAEs)in patients with malignant tumors,and to analyze the factors affecting blood concentration.Methods Blood concentration of patients with malignant tumors treated with tislelizumab was detected by liquid chromatography tandem mass spectrometry method,and the occurrence of irAEs during treatment was observed,and the correlation between blood concentration and irAEs was analyzed.At the same time,the diagnosis and treatment data of patients were collected to analyze the influence on blood drug concentration.Results Among the 50 malignant tumor patients treated with tislelizumab included in the analysis,34 cases developed irAEs,with an incidence of 68％,including hypothyroidism,rash,liver function impairment,etc.The mean blood concentration of 16.69 μg·mL-1 in the irAEs group was higher than that in the non-irAEs group of 8.41 μg·mL-1,and the difference was statistically significant(P＜0.05).The mean blood concentration of 20.98 μg·mL-1 in patients with hypothyroidism was higher than that in the group without hypothyroidism(11.04 μg·mL-1),and the mean blood concentration of 23.47 μg·mL-1 in patients with liver function damage was higher than that in the group without liver function damage(12.06 μg·mL-1),with statistical significance(all P＜0.05),and the threshold concentrations of associated risks were 14.61 and 13.19 μg·mL-1,respectively.At the same time,through the analysis of clinical characteristics of patients,the results showed that the mean blood concentration of 9.67 μg·mL-1 in the combined chemotherapy group was lower than that in the non-combined chemotherapy group(19.03μg·mL-1),and the blood concentration of 12.74 μg·mL- in the non-small cell lung cancer group was lower than that in the other groups(20.31 μg·mL-1),with statistical significance(all P＜0.05).Conclusion High blood concentration of tislelizumab can increase the risk of hypothyroidism and liver function damage in patients.
诸慧;原永芳;徐影
上海交通大学医学院附属第九人民医院药剂科,上海 200011上海交通大学医学院附属第九人民医院呼吸与危重症医学科,上海 200011
药学
替雷利珠单抗;免疫相关不良事件;治疗药物浓度监测;影响因素
tislelizumab;immune-related adverse event;therapeutic drug monitoring;influence factor
《中国临床药理学杂志》 2024 (008)
1217-1221 / 5
10.13699/j.cnki.1001-6821.2024.08.027
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