真实世界维奈克拉联合去甲基化药物治疗较高危骨髓增生异常综合征疗效及安全性分析

Efficacy and safety analysis of venetoclax combined with hypomethylating agents for the treatment of higher-risk myelodysplastic syndromes in the real world

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。

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 naive 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.