维奈克拉为基础的方案治疗急性髓系白血病疗效及生存分析  

Efficacy and Survival of Venetoclax Based Regimen in the Treatment of Acute Myeloid Leukemia

作　　者：孔繁聪[1] 齐凌[1] 黄文锋 喻敏[1] 周玉兰[1] 纪德香[1] 李菲[1] KONG Fan-Cong;QI Ling;HUANG Wen-Feng;YU Min;ZHOU Yu-Lan;JI De-Xiang;LI Fei(Center of Hematology,The First Affiliated Hospital of Nanchang University,Jiangxi Clinical Research Center for Hematologic Disease,Nanchang 330006,Jiangxi Province,China)

机构地区：[1]南昌大学第一附属医院血液病中心,江西省血液病临床医学研究中心,江西南昌330006

出　　处：《中国实验血液学杂志》2023年第6期1676-1683,共8页Journal of Experimental Hematology

基　　金：江西省科技创新基地项目(20212BCG74001,20211ZDG02006);江西省自然科学基金项目(20203BBGL73197,20224BAB206079);江西省卫健委项目(202210438)。

摘　　要：目的:探讨维奈克拉为基础(VEN-based)的方案治疗急性髓系白血病(AML)(非M3型)的疗效及生存情况。方法:回顾性分析2019年7月至2022年7月在南昌大学第一附属医院接受VEN-based方案治疗且至少完成1个疗程疗效评估的AML患者,分析患者的完全缓解(CR)/完全缓解伴血细胞计数未完全恢复(CRi)率、客观缓解率(ORR)及生存情况。结果:本研究共纳入79例患者,包括43例初治不适合强化疗(unfit)AML患者,36例复发难治(R/R)AML患者,中位年龄62(14-83)岁。总队列获得CR/CRi患者36例,ORR为64.6%。Unfit AML患者CR/CRi率明显高于R/R AML患者(60.5%vs27.8%,P=0.004)。Unfit AML各基因亚型患者均可从中获益,其中NPM1及IDH1/2突变患者获益最大,均有8例患者获得CR/CRi(8/9),微小残留病(MRD)转阴患者分别为7例(7/8)和5例(5/8);其次为TET2突变患者,6例获得CR/CRi(6/9),MRD转阴率为50%。R/R AML队列中,3例伴RUNX1突变患者中2例获得CR/CRi,MRD均未转阴,伴其他基因突变患者CR/CRi率均低于40%。中位随访时间为10.1(95%CI:8.6-11.6)个月,中位总生存(mOS)时间为9.1个月,无复发生存时间(RFS)未达到。Unfit AML患者mOS及RFS均明显长于R/R AML患者(14.1vs6.8个月,P=0.013;未达到vs3.3个月,P=0.000)。Unfit AML患者中伴NPM1和IDH1/2突变者mOS均未达到,无NPM1和IDH1/2突变患者mOS均为8个月(P=0.009;P=0.022);伴TP53突变者mOS明显短于无突变患者(5.2vs14.1个月,P=0.049)。R/R AML患者中各基因亚型突变与未突变患者间mOS均无显著差异(P> 0.05)。所有患者均发生血液学不良反应,91.1%患者血液学AE分级≥3级;非血液学不良反应最常见为感染,发生率为91.1%,VEN-based方案总体耐受性好。结论:VENbased的方案尤其在初治unfit患者中,可以获得高应答率,且安全性可接受。该方案在伴NPM1、IDH1/2基因突变的unfit AML患者中疗效显著,这部分患者可快速获得MRD转阴,且生存期延长。Objective:To explore the efficacy and survival of venetoclax based(VEN-based)regimen in the treatment of acute myeloid leukemia(AML).Methods:A retrospective study was conducted in patients who received VEN-based regimen and completed at least1course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July2019to July2022.The incidence of complete remission(CR)/CR with incomplete hematologic recovery(CRi)rate,objective remission rate(ORR)and survival of patients with different risk stratification and gene subtypes were analyzed.Results:A total of79patients were enrolled,including43patients with newly diagnosed unfit AML(unfit AML)and36relapsed/refractory AML(R/R AML).The median age of the patients was62(14-83)years old.36out of79patients achieved CR/CRi and the ORR of the whole cohort was64.6%.The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients(60.5% vs27.8%,P=0.004).In unfit AML cohort,the patients with NPM1 and IDH1/2 mutations were benefited,8out of9patients ahcieved CR/CRi,7/8and5/8patients achieved minimal residual disease(MRD)negativity,respectively.Six out of9patients with TET2mutation achieved CR/CRi,3/6patients achieved MRD negativity.In R/R AML cohort,2out of3patients with RUNX1 mutation achieved CR/CRi,without MRD negative,while the CR/CRi rate of patients with other gene mutations was lower than40%.The median follow-up time was10.1(95% CI:8.6-11.6)months.In whole cohort,the median overall survival(mOS)time was9.1months and the relapse free survival(RFS)time was not reached.The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients(14.1vs6.8months,P= 0.013;not reached vs3.3months,P= 0.000).In unfit AML cohort,the mOS of patients with NPM1or IDH1/2 mutations was not reached,while that of patients without NPM1 or IDH1/2 mutations was8.0months(P=0.009;P= 0.022).Furthermore,the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation(5.2vs14.1months,P

关 键 词：急性髓系白血病 维奈克拉 疗效 生存分析 

分 类 号：R733.71[医药卫生—肿瘤]