The value of venetoclax blood concentration monitoring in the treatment of acute myeloid leukemia and the efficacy and safety of combined azacytidine in the treatment of acute myeloid leukemia
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摘要: 目的评价维奈克拉血药浓度对治疗急性髓系白血病(AML)疗效及安全性的影响，并分析维奈克拉联合阿扎胞苷治疗AML的疗效与安全性。方法回顾性分析2020年7月—2021年12月我院接受维奈克拉联合治疗的40例AML患者的临床资料，维奈克拉血药浓度检测采用HPLC-MS/MS法。结果随访2.5~17.5个月，中位随访6.1个月。总缓解率为70.0%(28/40)，其中16例(40.0%)获得完全缓解，8例(20.0%)获得骨髓完全缓解伴不完全血液学恢复，4例(10.0%)获得部分缓解。发生Ⅲ~Ⅳ级中性粒细胞减少、血小板计数下降的患者分别为23例(57.5%)和22例(55.0%)，1例患者因Ⅲ~Ⅳ级血液学毒性和感染而停药，无临床肿瘤溶解综合征发生。40例患者的中位维奈克拉血药浓度为1.6(0.2~7.8)μg/mL，血药浓度 < 1.0 μg/mL、1.0~3.2 μg/mL、>3.2 μg/mL组的总有效率分别为36.4%(4/11)、89.5%(17/19)、70.0%(7/10)，≥Ⅲ级中性粒细胞减少的发生率分别为36.4%(4/11)、47.4%(9/19)、100.0%(10/10)，≥Ⅲ级血小板计数降低的发生率分别为45.5%(5/11)、42.1%(8/19)、90.0%(9/10)。维奈克拉血药浓度与中性粒细胞计数(R2=0.485)及血小板计数(R2=0.457)存在一定的线性关系(均P < 0.05)。40例患者中15例(37.5%)死亡，中位总生存期为10.1(0.3~17.5)个月。结论维奈克拉联合阿扎胞苷较维奈克拉单药治疗缓解率高，总生存时间长，且严重不良反应少。监测维奈克拉血药浓度可以提高用药安全性，减少不良反应的发生。Abstract: ObjectiveTo evaluate the efficacy and safety of venetoclax in the treatment of acute myeloid leukemia(AML), and to analyze the efficacy and safety of venetoclax combined with azacytidine in the treatment of AML.MethodsClinical data of 40 patients with AML who received venetoclax combination therapy in our hospital from July 2020 to December 2021 were retrospectively analyzed. Plasma concentration of venetoclax was determined by HPLC-MS/MS.ResultsThe median follow-up time was 6.1(2.5 to 17.5) months. The overall response rate was 70.0%(28/40), of which 16 cases(40.0%) achieved complete response, 8 cases(20.0%) achieved complete response with incomplete hematologic recovery, and 4 cases(10.0%) achieved partial response. There were 23 cases(57.5%) and 22 cases(55.0%) with grade Ⅲ-Ⅳ neutropenia and thrombocytopenia, respectively. One case stopped medication due to grade Ⅲ-Ⅳhematological toxicity and infection. There was no clinical tumor lysis syndrome. The median plasma concentration of venetoclax in 40 patients was 1.6(0.2-7.8) μg/mL. In groups of venetoclax concentration < 1.0 μg/mL, 1.0-3.2 μg/mL, >3.2 μg/mL, the overall response rate was 36.4%(4/11), 89.5%(17/19) and 70.0%(7/10), the incidence of grade ≥Ⅲ neutropenia was 36.4%(4/11), 47.4%(9/19) and 100.0%(10/10), and the incidence of grade ≥Ⅲ thrombocytopenia was 45.5%(5/11), 42.1%(8/19) and 90.0%(9/10), respectively. There was a certain linear relationship between the serum concentration of venetoclax and neutrophil count(R2=0.485, P < 0.05) and platelet count(R2=0.457, P < 0.05). Among the 40 patients, 15 cases(37.5%) died, and the median overall survival was 10.1(0.3-17.5) months.ConclusionCompared with venetoclax monotherapy, venetoclax combined with azacytidine has a higher remission rate, longer overall survival time, and less serious adverse events. Monitoring the blood concentration of venetoclax can improve drug safety and reduce adverse events.
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Key words:
- acute myeloid leukemia /
- venetoclax /
- azacitidine /
- curative effect /
- blood concentration
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表 1 患者临床特征与CR的相关性分析
例 临床特征 获得CR
(16例)未获得CR
(24例)P 年龄 < 60岁 7 11 1.00 ≥60岁 9 13 性别 男 8 13 1.00 女 8 11 既往治疗次数 0 6 8 0.81 < 3次 5 8 ≥3次 5 8 维奈克拉总疗程 < 3个 11 21 0.29 ≥3个 5 3 移植情况 否 15 24 0.83 是 1 0 预后情况 预后良好 7 3 0.79 预后中等 1 7 预后不良 8 14 
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表 2 维奈克拉最高血药浓度不同分组的临床疗效及不良反应比较
维奈克拉血药浓度 例数 ORR/例(%) 不良反应/例(%) ≥Ⅲ级中性粒细胞减少 ≥Ⅲ级血小板计数降低 < 1.0 μg/mL 11 4(36.4) 4(36.4) 5(45.5) 1.0~3.2 μg/mL 19 17(89.5) 9(47.4) 8(42.1) >3.2 μg/mL 10 7(70.0) 10(100.0) 9(90.0)
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