恶性黑色素瘤患者经帕博利珠单抗治疗后发生免疫相关肝毒性的影响因素及预测模型的建立  

Influence factors and prediction model of immune-mediated hepatotoxicity in patients with malignant melanoma treated with pembrolizumab

作　　者：尹月[1] 赵志刚[2] 张艳华[1] YIN Yue;ZHAO Zhi-gang;ZHANG Yan-hua(Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Peking University Cancer Hospital&Institute,BEIJING 100142,China;Department of Pharmacy,Bejing Tiantan Hospital Affliated to Capital Medical University,BEIJING 100050,China)

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所,恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142 [2]首都医科大学附属北京天坛医院药剂科,北京100050

出　　处：《中国新药与临床杂志》2022年第8期490-494,共5页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：目的探讨恶性黑色素瘤(MM)患者经帕博利珠单抗治疗后发生免疫相关肝毒性(IMH)的影响因素,构建预测模型。方法选取使用帕博利珠单抗治疗的MM患者126例,收集患者的临床资料,包括性别、年龄、合并基础疾病、体表面积、分期等,采用单因素分析和多因素logistic回归分析确定帕博利珠单抗治疗发生IMH的危险因素,并建立预测模型。采用受试者操作特征(ROC)曲线评价预测模型。结果126例病例中共发生不良反应91例(72.2%),其中IMH 24例(19.0%)。经logistic回归分析显示,IMH影响因素包括有无肝病(OR=2.072)、疗程(OR=1.459)、合并化疗或化疗+靶向药物(OR=0.005)、治疗前血红蛋白水平(OR=0.124)、合并靶向药物(OR=0.106)。ROC曲线下面积为0.934±0.022(95%CI:0.891~0.978),预测特异度为75%,敏感度为100%,准确度阳性预测值为70.8%,阴性预测值为94.6%。当预测模型方程logit(P)≥0.093592时,可作为判断使用帕博利珠单抗后是否发生IMH的标准。结论患者基础肝病情况、疗程、合并化疗或靶向药物、治疗前血红蛋白水平是使用帕博利珠单抗发生IMH的影响因素,拟合的预测模型检验结果可靠。AIM To investigate the influencing factors of immune-mediated hepatotoxicity(IMH)in patients with malignant melanoma(MM)treated with pembrolizumab,and to construct a predictive model.METHODS A total of 126 MM patients treated with pembrolizumab were selected,and the clinical data of the patients,including gender,age,underlying diseases,body surface area and stage,etc.,were retrospectively analyzed.Univariate analysis and multivariate logistic regression analysis were used to determine the risk factors for IMH after pembrolizumab treatment.And the prediction model was established.The receiver operating characteristic(ROC)curve was used to evaluate the prediction model.RESULTS A total of 91 cases(72.2%)adverse drug reactions occurred in 126 cases,including 24 cases(19.0%)of IMH.Logistic regression analysis showed that the influencing factors of IMH included liver disease(OR=2.072),course of treatment(OR=1.459),combined chemotherapy or chemotherapy+targeted drugs(OR=0.005),hemoglobin before treatment(OR=0.124),combined targeted drugs(OR=0.106).The AUC under ROC curve was 0.934±0.022(95%CI:0.891 to 0.978).The predictive specificity was 75%,the sensitivity was 100%,the accuracy positive predictive value was 70.8%,the negative predictive value was 94.6%.When logit(P)≥0.093592,it can be used as the diagnostic criteria for judging whether IMH occurs after using pembrolizumab.CONCLUSION Patients with underlying liver disease situation,course of treatment,combined chemotherapy or targeted drugs,and hemoglobin level before treatment are the influencing factors of IMH with pembrolizumab,and the prediction model test results are reliable.

关 键 词：黑色素瘤 帕博利珠单抗 程序性细胞死亡受体1 免疫疗法 药物不良反应 化学性与药物性肝损伤 影响因素分析 

分 类 号：R979.5[医药卫生—药品]