Gao Q Y, Li B, Qu S Q, Pan L J, Jiao M, Zhao J Y, Xu Z F, Xiao Z J, Qin T J
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China Tianjin Institutes of Health Science, Tianjin 301600, China.
Zhonghua Xue Ye Xue Za Zhi. 2024 Feb 14;45(2):156-162. doi: 10.3760/cma.j.cn121090-20230926-00136.
To investigate the efficacy and safety of combining venetoclax (VEN) with hypomethylated drugs (HMA) in the treatment of higher-risk (IPSS-R score >3.5) myelodysplastic syndromes (MDS) . From March 2021 to December 2022, forty-five MDS patients with intermediate and high risk were treated with VEN in combination with HMAs. Clinical data were collected and analyzed retrospectively, including gender, age, MDS subtype, IPSS-R score, treatment regimen, and efficacy, etc. Kaplan-Meier method and Cox regression model were used to analyze univariate and multivariate of survival prognosis. ①Forty-five patients with MDS, including ninety-one percent were classified as high or very high risk. According to the 2023 consensus proposal for revised International Working Group response criteria for higher-risk MDS, the overall response rate (ORR) was 62.2% (28/45), with the complete response rate (CR) was 33.3% (15/45). For twenty-five naïve MDS, the ORR was 68% (17/25) and the CR rate was 32% (8/25). In nonfirst-line patients, the ORR and CR were 55% (11/20) and 35% (7/20) respectively. The median cycle to best response was 1 (1-4). ②With a median followup of 189 days, the median overall survival (OS) time was 499 (95% confidence interval, 287-711) days, and most patients died from disease progression. Responders had a significantly better median OS time than nonresponders (499 days 228 days, <0.001). Multifactor analysis revealed that IPSS-R score and response to treatment were independent prognostic factors for OS; the presence of SETBP1 gene mutations was associated with a longer hospital stay (51.5 days 27 days, =0.017) . There is clinical benefit of venetoclax in combination with hypomethylated agents in patients with higher-risk MDS, but adverse events such as severe hypocytopenia during treatment should be avoided.
探讨维奈克拉（VEN）联合去甲基化药物（HMA）治疗高危（国际预后评分系统修订版[IPSS-R]评分>3.5）骨髓增生异常综合征（MDS）的疗效和安全性。2021年3月至2022年12月，45例中高危MDS患者接受了VEN联合HMA治疗。回顾性收集并分析临床资料，包括性别、年龄、MDS亚型、IPSS-R评分、治疗方案及疗效等。采用Kaplan-Meier法和Cox回归模型分析生存预后的单因素和多因素情况。①45例MDS患者中，91%被归类为高危或极高危。根据2023年修订的国际工作组高危MDS反应标准共识建议，总缓解率（ORR）为62.2%（28/45），完全缓解率（CR）为33.3%（15/45）。25例初治MDS患者的ORR为68%（17/25），CR率为32%（8/25）。非一线治疗患者的ORR和CR分别为55%（11/20）和35%（7/20）。达到最佳反应的中位周期数为1（1 - 4）。②中位随访189天，中位总生存期（OS）为499天（95%置信区间，287 - 711天），大多数患者死于疾病进展。缓解者的中位OS时间显著长于未缓解者（499天对228天，P<0.001）。多因素分析显示，IPSS-R评分和治疗反应是OS的独立预后因素；SETBP1基因突变与住院时间延长相关（51.5天对27天，P = 0.017）。维奈克拉联合去甲基化药物对高危MDS患者有临床益处，但应避免治疗期间严重血细胞减少等不良事件。
