维奈克拉联合阿扎胞苷治疗复发/难治性急性髓细胞白血病患者的疗效和安全性评价

Evaluation of efficacy and safety of venetoclax combined with azacytidine in treatment of patients with relapsed/refractory acute myeloid leukemia

目的探讨维奈克拉(VEN)联合阿扎胞苷(AZA)治疗复发/难治性急性髓细胞白血病(R/R AML)患者的疗效和安全性。方法选择2020年4月14日至2022年3月4日于成都市第三人民医院血液科住院的7例接受VEN联合AZA治疗R/R AML患者为研究对象。其中,男性患者为4例,女性为3例;患者中位年龄为45岁(37,46岁)。采用回顾性研究方法,收集所有患者年龄、性别、血常规、染色体、融合基因、基因突变及预后分层等临床资料。1个疗程VEN联合AZA治疗结束后,对患者进行疗效及安全性评价。采用Kaplan-Meier法绘制患者的总体生存(OS)和无病生存(DFS)曲线。本研究遵循的程序符合2013年修订版《世界医学协会赫尔辛基宣言》要求。结果①本组患者中,染色体异常核型者为4例[3例为复杂核型和1例为46,XX,inv(16)(p13q22)],融合基因阳性者为1例(CBFβ-MYH11融合基因),伴基因突变者为6例(TP53、IDH1/2和FLT3突变等),预后良好、中等、不良者分别为2、2、3例。②本组患者总体反应率(ORR)为85.7%(6/7),完全缓解(CR)、部分缓解(PR)者分别为5例和1例。治疗前预后分层系预后良好、中等与不良患者中,获得CR者分别为2、1、2例;获得CR后进行异基因造血干细胞移植(allo-HSCT)者为3例,未移植者为4例;再复发患者为4例。③本组患者均发生≥3级血液学不良反应,5例发生非血液学不良反应,无一例患者因不良反应而停药。④本组患者6个月、1年OS和DFS率分别为71.4%和57.1%、42.9%和14.3%。3例CR后接受allo-HSCT患者的OS期分别为13、13、14个月。结论VEN联合AZA方案治疗R/R AML患者,特别是伴TP53、IDH1/2和FLT3突变者的疗效显著,或可作为其具有临床前景的治疗选择。

ObjectiveTo explore the efficacy and safety of venetoclax(VEN)combined with azacytidine(AZA)in treatment of relapsed/refractory acute myeloid leukemia(R/R AML).MethodsFrom April 14,2020 to March 4,2022,seven R/R AML patients hospitalized in the Hematology Department of Chengdu Third People′s Hospital were selected as the research subjects.Among them,there were 4 male and 3 females;the median age of the patients was 45 years(37,46 years).A retrospective study method was used to collect clinical data such as age,gender,blood routine,chromosomes,fusion genes,gene mutations and prognosis stratification of all patients.The efficacy and safety will be evaluated after one course of treatment with VEN combined with AZA regimen.The Kaplan-Meier method was used to draw the overall survival(OS)and disease-free survival(DFS)curves of patients.The procedures followed in this study were in line with the requirements of Helsinki Declaration of the World Medical Association revised in 2013.Results①There were 4 patients who had abnormal chromosomal karyotype[3 cases of complex karyotype and 1 case of 46,XX,inv(16)(p13q22)].One patient had a positive fusion gene(CBFβ-MYH11 fusion gene);6 patients had gene mutations(TP53,IDH1/2 and FLT3 mutations,etc.).There were 2,2 and 3 cases with favorable,intermediate and adverse prognosis,respectively.②The overall response rate(ORR)of patients was 85.7%(6/7),and 5 cases of complete remission(CR)and 1 case of partial remission(PR).The number of CR patients of favorable,intermediate and adverse prognosis were 2,1,and 2,respectively.There were 3 patients underwent allo-HSCT after CR.Re-relapse occurred in 4 patients.③All patients in this group experienced≥3 grade hematological adverse reactions.Non-hematological adverse reactions occured in 3 patients.No patient discontinued the drug due to adverse reactions.④The 6-month and 1-year OS and DFS rates were 71.4%and 57.1%,42.9%and 14.3%,respectively.The OS time of 3 patients who underwent allo-HSCT were 13,13,and 14 months respectively.ConclusionsThe VEN combined with AZA regimen has significant efficacy in the treatment of R/R AML patients,especially in those patients with TP53,IDH1/2 and FLT3 mutations,and can be used as their clinically promising treatment option.