维奈克拉联合阿扎胞苷治疗急性髓系白血病患者中维奈克拉血药浓度监测及与疗效关系  

Therapeutic drug monitoring of venetoclax in Chinese acute myeloid leukemia patients using venetoclax combined with azacitidine

作　　者：王昀琪 王慧芳 付强 刘开彦[1] 江倩[1] 江浩[1] 黄晓军[1,2,3] 唐菲菲 WANG Yunqi;WANG Huifang;FU Qiang;LIU Kaiyan;JIANG Qian;JIANG Hao;HUANG Xiaojun;TANG Feifei(Peking University People's Hospital,Peking University Institute of Hematology,National Clinical Research Center for Hematologic Disease,Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation,Beijing,100044,China;Peking-Tsinghua Center for Life Sciences,Academy for Advanced Interdisciplinary Studies,Peking University;State Key Laboratory of Natural and Biomimetic Drugs,Peking University)

机构地区：[1]北京大学人民医院,北京大学血液病研究所,国家血液系统疾病临床医学研究中心,造血干细胞移植治疗血液病北京市重点实验室,北京100044 [2]北大-清华生命科学联合中心,前沿交叉学科研究院 [3]天然药物及仿生药物全国重点实验室

出　　处：《临床血液学杂志》2024年第9期643-648,656,共7页Journal of Clinical Hematology

基　　金：国家重点研发计划资助项目(No:2021YFC2500302)。

摘　　要：目的探讨维奈克拉(venetoclax,VEN)联合阿扎胞苷(azacitidine,AZA)治疗中国急性髓系白血病(acute myeloid leukemia,AML)患者中VEN血药浓度监测以及与疗效的关系。方法回顾性分析2021年4月至2023年2月于北京大学血液病研究所接受VEN联合AZA治疗和持续性VEN血药浓度监测的38例初治不适合强化疗(unfit)及难治/复发(R/R)AML患者。分析真实世界中国人群第1个疗程VEN联合AZA诱导治疗AML期间持续性监测d4、d7、d14、d21、d28 VEN谷浓度及与疗效的关系,以及与可能影响VEN血药浓度的基线患者情况和基线临床特征的相关性。结果入组38例AML患者,初治unfit AML 21例(55.3%),R/R AML 17例(44.7%),中位年龄51.5(16~70)岁,男19例(50.0%),中位随访时间18.9(5.5~28.1)个月。所有患者均因联合应用伏立康唑而调整VEN剂量为100 mg Qd。根据2022 ELN标准进行危险分层,初治unfit组高危15例(71.4%),R/R组高危9例(52.9%)。初治unfit组VEN联合AZA中位治疗疗程为1(1~5)个,R/R组VEN联合AZA中位治疗疗程为1(1~2)个。经1个疗程VEN联合AZA治疗后,初治unfit AML患者14例(66.7%)达完全缓解/血细胞计数未完全恢复的完全缓解(CR/CRi),4例(19.0%)达部分缓解(PR),总体反应率达85.7%(18/21)。R/R AML患者6例(35.3%)达CR/CRi,4例(23.5%)达PR,总体反应率达58.8%(10/17)。初治unfit组诱导期间VEN稳态谷浓度Cmin在d4、d7、d14、d21、d28分别为1330(299~6570)ng/mL、2158(264~5050)ng/mL、2404(533~5760)ng/mL、2752(282~4850)ng/mL、2251(560~4410)ng/mL。R/R组再诱导期间VEN稳态谷浓度Cmin分别为1203(692~3100)ng/mL、2245(799~5580)ng/mL、1950(890~4920)ng/mL、1856(473~3210)ng/mL、1650(934~2584)ng/mL。结果显示VEN谷浓度Cmin在初治unfit组(P=0.23)及R/R组(P=0.24)有反应与未缓解组间均差异无统计学意义。VEN谷浓度与患者基线特征(性别、年龄、身高、体重、体重指数、体表面积)及基线临床特征(白蛋白、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、�Objective To investigate the monitoring of drug plasma concentration of venetoclax(VEN)and its relationship with therapeutic efficacy in Chinese acute myeloid leukemia(AML)patients receiving VEN combined with azacitidine(AZA).Methods A total of 38 AML patients receiving VEN+AZA and undergoing continuous VEN drug plasma concentration monitoring between April 2021 and February 2023 at Peking University Institute of Hematology were retrospectively analyzed.We analyzed continuously monitoring VEN trough concentration on d4,d7,d14,d21 and d28 during the first course of VEN+AZA induction therapy for AML in the real-world Chinese population and its relationship with therapeutic effect,as well as the correlation with the baseline patient conditions and clinical characteristics that may influence VEN drug plasma concentration.Results A total of 38 AML patients were enrolled,including 21(55.3%)unfit de novo AML cases and 17(44.7%)R/R AML cases.The median age was 51.5 years(range 16-70 years),and 19 patients(50.0%)were male.The median follow-up time was 18.9 months(range 5.5-28.1 months).All patients received VEN at an adjusted dose of 100 mg Qd due to the combination of voriconazole.According to the 2022 ELN risk group classification,15 patients(71.4%)in the unfit de novo AML group were high-risk group,and 9 patients(52.9%)in R/R AML group were high-risk group.The median treatment duration was 1 course(range 1-5 courses)for the unfit de novo AML group and 1 course(range 1-2 courses)for R/R AML group.After one cycle of VEN+AZA,for the unfit de novo AML group,14 patients(66.7%)achieved complete remission(CR)/CR with incomplete hematological recovery(CRi),and 4 patients(19.0%)achieved partial remission(PR),with an overall response rate(ORR)of 85.7%(18/21).For R/R AML group,six patients(35.3%)achieved CR/CRi,4 patients(23.5%)achieved PR,and the ORR was 58.8%(10/17).The VEN steady-state Cmin of unfit patients during induction therapy were 1330(299-6570)ng/mL,2158(264-5050)ng/mL,2404(533-5760)ng/mL,2752(282-4850)ng/mL,2251(560-4

关 键 词：急性髓系白血病 维奈克拉 血药浓度监测 血药浓度 

分 类 号：R733.71[医药卫生—肿瘤]