性别和年龄对利妥昔单抗治疗弥漫大B细胞淋巴瘤患者的影响研究  

Effect of gender and age on rituximab therapy for diffuse large B-cell lymphoma

作　　者：刘澍[1] 黄河[1] 张璋[1] 陈卓佳[1] 王钊 方小洁 管少兴 王雪丁[2] 刘韬[1] 黄红兵[1] 林桐榆[1,3] 黄民 LIU Shu;HUANG He;ZHANG Zhang;CHEN Zhuo-jia;WANG Zhao;FANG Xiao-jie;GUAN Shao-xing;WANG Xue-ding;LIU Tao;HUANG Hong-bing;LIN Tong-yu;HUANG Min(Department of Pharmacy,State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,SunYat-sen University Cancer Center,Guangzhou 510060,Guangdong Province,China;Institute of Clinical Pharmacology,School of Pharmaceutical Sciences,Sun Yat-sen University,510006,Guangdong Province;Department of Medical Sichuan Cancer Hospital&Institute,Sichuan Cancer Center,Schoolof Medicine,Universityof Electronic Science and Technology of China,Chengdu 610041,Sichuan Province,China)

机构地区：[1]中山大学肿瘤防治中心药学部,华南肿瘤学国家重点实验室,肿瘤医学协同创新中心,广东广州510060 [2]中山大学药学院临床药理研究所,广东广州510006 [3]四川省肿瘤医院(研究所),四川省癌症防治中心,电子科技大学医学院附属肿瘤医院肿瘤内科,四川成都610041

出　　处：《中国临床药理学杂志》2022年第20期2406-2410,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金重点基金资助项目(81730103);广东省医学科学技术研究基金资助项目(A2021159);广东省医院协会药学科研专项基金资助项目(2021YXZD03);广东省科学技术厅创省科技创新战略专项基金资助项目(2020B1212060034);国家自然科学基金青年基金资助项目(82204532)。

摘　　要：目的 拟通过血药浓度监测验证并探索相关机制,以指导利妥昔单抗个体化的剂量调整。方法 开展前瞻性临床试验入组99例初治的弥漫大B细胞淋巴瘤(DLBCL)患者,以酶联免疫法检测利妥昔单抗浓度,分析药物浓度与疗效的相关性,及年龄、性别、肿瘤分期对浓度和疗效的影响。结果 R-CHOP方案一线化疗的响应率高达82.83%,半年、1年肿瘤进展率分别为11.11%和15.15%,利妥昔单抗谷浓度的均值为(21.00±8.12)μg·mL^(-1)。年龄≥70岁患者1年肿瘤进展率显著增高至60.00%,患者利妥昔单抗谷浓度均值显著降低至(13.37±6.69)μg·mL^(-1)。男性患者1年肿瘤进展率显著增高至21.82%,患者利妥昔单抗谷浓度对比女性有降低趋势。肿瘤分期Ⅳ期患者1年肿瘤进展率显著增高至30.30%,患者药物谷浓度均值显著降低至(17.07±8.93)μg·mL^(-1)。依据患者肿瘤分期、年龄、性别进行分层分析,发现Ⅳ期且年龄≥65的女性、Ⅳ期年龄<65的男性、Ⅳ期年龄≥65的男性1年肿瘤进展率分别为40%,41.67%,50%,显著高于其他患者。同时,3组患者利妥昔单抗谷浓度分别为(13.57±8.43),(17.09±6.50),(10.93±5.98)μg·mL^(-1),显著低于其他患者。结论 肿瘤Ⅳ期且年龄≥65的女性及Ⅳ期男性临床疗效不理想,体内利妥昔单抗浓度较低,推荐适当增加给药剂量。Objective Some clinical trials have shown that female lymphoma patients receiving rituximab contained regimen benefit more than elderly male patients. The aim of this study was to verify this phenomenon and to explore the relevant mechanism through therapeutic drug monitoring and then to guide the dosage adjustment for rituximab. Methods A prospective clinical trial was conducted and 99 patients with newly diagnosed diffuse large B-cell lymphoma(DLBCL) were enrolled, the concentration of rituximab was detected by enzyme linked immunosorbent assay, and the association between the drug concentration and clinical outcomes, the influence of age, gender and tumor stage on rituximab concentration and outcomes were analyzed. Results The treatment response rate of the first-line R-CHOP regimen was as high as 82.83%;the tumor progression rates for half a year and one year were 11.11% and 15.15, respectively;the mean trough concentration of rituximab was(21.00±8.12) μg·mL. The one-year tumor progression rate of patients ≥70 years was significantly increased to 60. 00% and the trough concentration of patients with aged ≥ 70 years was significantly decreased to( 13. 37 ± 6. 69)μg·mL^(-1)-1. The one-year tumor progression rate of male patients was significantly increased to 21. 82%,and the rituximab concentration of male patients also tended to be lower than that in female patients. The one-year tumor progression rate of patients with stage Ⅳ disease was significantly increased to 30. 30%,and the drug concentration was significantly reduced to( 17. 07 ± 8. 93) μg·mL. A stratified analysis based on the patient’s tumor stage,age,and gender was further conducted,the one-year tumor progression rates of women with Ⅳ stage and age≥ 65,men with stage Ⅳ and age < 65 and men with stage Ⅳ and age ≥65 were 40%,41. 67% and 50%,respectively,which were significantly higher than those in other patients,meanwhile,the trough concentrations of rituximab in the three groups were( 13. 57 ± 8. 43),( 17. 09 ± 6. 50) an

关 键 词：利妥昔单抗 弥漫大B细胞淋巴瘤 药物浓度 年龄 性别 

分 类 号：R979.1[医药卫生—药品]