Objective: 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) . Methods: 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. Results: 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 vs 228 days, P<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 vs 27 days, P=0.017) . Conclusions: 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.
目的： 探讨维奈克拉（VEN）联合去甲基化药物（HMA）治疗较高危[修订后国际预后评分系统（IPSS-R）评分>3.5分]的骨髓增生异常综合征（MDS）的疗效及安全性。 方法： 纳入2021年3月至2022年12月于中国医学科学院血液病医院连续收治的共计45例应用VEN联合HMA方案治疗的较高危MDS患者，回顾性收集并分析临床资料，主要包括性别、年龄、MDS亚型、IPSS-R评分、治疗方案及疗效等，采用Kaplan-Meier法和Cox回归模型进行生存预后的单因素及多因素分析。 结果： ①共计45例MDS患者，其中91%患者为IPSS-R评分高危或极高危患者。按照国际工作组（IWG）2023版修订评价标准：总缓解率（ORR）为62.2%（28/45），完全缓解（CR）率为33.3%（15/45）。25例初治患者ORR为68%（17/25），CR率为32%（8/25）。20例非初治MDS患者ORR为55%（11/20），CR率为35%（7/20）。患者达最佳疗效中位周期数为1（1～4）个。②中位随访时间189 d，中位总生存（OS）期为499（95% CI 287～711）d，患者死亡多因本病进展。VEN应答者中位OS期明显长于无应答者（499 d对228 d，P<0.001）。③多因素分析显示IPSS-R评分、对治疗反应为影响OS的独立预后因素；存在SETBP1基因突变可能延长患者住院时间（51.5 d对27 d，P＝0.017）。 结论： VEN联合HMA治疗较高危MDS患者存在临床获益，但需警惕治疗过程中发生严重血细胞减低等不良反应。.
Keywords: Hypomethylating agents; Myelodysplastic syndromes; Real world; Venetoclax.