摘要
目的评估维奈克拉(VEN)联合去甲基化药物(HMA)治疗较高危骨髓增生异常综合征(HR-MDS)的疗效和安全性,并分析可能影响疗效的因素。方法回顾性分析2019年11月至2023年5月在郑州大学第一附属医院血液科确诊的83例HR-MDS患者的临床资料,所有患者在治疗期间均应用过VEN+HMA治疗。生存曲线采用Kaplan-Meier法绘制,组间生存比较采用Log-rank检验。结果83例HR-MDS患者中,男性51例(61.4%),中位年龄57(15~82)岁。其中,初始治疗MDS患者45例(54.2%),应用HMA≤4个疗程患者23例(27.7%),HMA治疗失败15例(18.1%)。中位随访10.3(0.6~34.4)个月,总体反应率(ORR)62.7%(52/83),其中18例(21.7%)获完全缓解(CR),14例(16.9%)获骨髓完全缓解(mCR)并血液学改善,20例(24.1%)获mCR。初始治疗、应用HMA≤4个疗程、HMA治疗失败3组患者的ORR分别为66.7%、60.9%、53.3%(P=0.641)。中位总生存(OS)期14.6(95%CI 7.2~22.0)个月,中位无进展生存(PFS)期8.9(95%CI 6.7~11.1)个月。多因素分析显示,碱性磷酸酶(ALP)≥90 U/L(OR=14.574,95%CI 3.036~69.951,P=0.001)、TP53突变(OR=13.052,95%CI 1.982~85.932,P=0.008)和U2AF1突变(OR=7.720,95%CI 1.540~38.698,P=0.013)是VEN+HMA治疗无效的独立危险因素。所有患者均发生了血液学不良事件(AE),因治疗所致3~4级白细胞减少的发生率最高,为48.2%(40/83)。最常见的非血液AE为肺部感染(31.3%)。结论VEN+HMA在初始治疗及HMA治疗失败的HR-MDS患者中均有较高的治疗反应率,ALP≥90 U/L、TP53突变和U2AF1突变是无治疗反应的独立危险因素。
Objective This study aimed to evaluate the efficacy and safety of venetoclax(VEN)combined with hypomethylating agents(HMA)in the treatment of higher-risk myelodysplastic syndromes(HR-MDS)and analyze the factors influencing their therapeutic effect.Methods The clinical data of 83 patients with HR-MDS who were diagnosed at the First Affiliated Hospital of Zhengzhou University between November 2019 and May 2023 were retrospectively analyzed.All patients were treated with VEN combined with HMA.The Kaplan-Meier method was used to depict the survival curves,and the log-rank test was used to compare survival between the groups.Results The median age was 57(15-82)years old,and 51 patients(61.4%)were male.Forty-five patients(54.2%)were initially treated with HMA,23(27.7%)received≤4 cycles of HMA,and 15(18.1%)demonstrated HMA failure.At the median follow-up of 10.3(0.6-34.4)months,the overall response rate(ORR)was 62.7%(52/83),including 18 patients(21.7%)with a complete response(CR),14(16.9%)with a bone marrow CR(mCR)with hematological improvement,and 20(24.1%)with a mCR.The ORR of patients with initial treatment,≤4 HMA cycles,and HMA failure were 66.7%,60.9%,and 53.3%,respectively(P=0.641).The median overall survival time was 14.6(95%CI 7.2-22.0)months,and the median progression-free survival time was 8.9(95%CI 6.7-11.1)months.The multivariate analysis showed that serum alkaline phosphatase(ALP)≥90 U/L(OR=14.574,95%CI 3.036-69.951,P=0.001),TP53 mutation(OR=13.052,95%CI 1.982-85.932,P=0.008),and U2AF1 mutation(OR=7.720,95%CI 1.540-38.698,P=0.013)were independent risk factors for poor efficacy of VEN combined with HMA.Hematological toxicity occurred in all patients,and the incidence of treatment-induced grade 3-4 leukopenia was 48.2%(40/83).Infection was the most common non-hematological adverse event,mainly pulmonary infection(31.3%).Conclusion VEN combined with HMA had a high response rate in patients with HR-MDS,both at initial treatment and with HMA failure.ALP≥90 U/L,TP53 mutation,and U2AF1 mutation were indepe
作者
刘柳
和凤
徐衍
李涛
李亚飞
汤平
孙玲
Liu Liu;He Feng;Xu Yan;Li Tao;Li Yafei;Tang Ping;Sun Ling(Department of Hematology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2024年第3期277-283,共7页
Chinese Journal of Hematology
