维奈克拉联合阿扎胞苷治疗急性髓系白血病近期效果观察

Short-term efficacy observation of venetoclax combined with azacitidine in treatment of patients with acute myeloid leukemia

目的探讨维奈克拉(Ven)联合阿扎胞苷(AZA)治疗初治及复发难治急性髓系白血病(AML)的近期临床效果。方法回顾性分析2020年4月至2022年6月在南京中医药大学附属苏州市中医医院接受Ven+AZA治疗的18例初治及复发难治AML患者资料。分析初治和复发难治及不同基因突变患者完全缓解或血细胞计数未完全恢复的完全缓解(CR/CRi)情况及客观缓解率(ORR)[以CR/CRi+部分缓解(PR)计算]。随访截至2022年6月30日,分析复发难治患者总生存(OS)情况。总结不良反应发生情况。结果 18例患者中位年龄58岁(23~81岁),男性8例,女性10例;初治6例,复发难治12例;中位随访时间3个月(1~15个月)。6例初治患者经1个周期Ven+AZA治疗后,5例达CR/CRi,ORR为83.3%(5/6);12例复发难治患者经1个周期Ven+AZA治疗后,5例达CR/CRi,3例PR,ORR为66.7%(8/12)。18例患者中,FLT3-ITD/TKD突变7例,1个周期Ven+AZA治疗后,其中1例达CR/CRi,1例PR,ORR为28.6%(2/7);NPM1突变3例,均合并FLT3-ITD/TKD突变,其中1例达CR/CRi,ORR为33.3%(1/3);IDH1/2突变4例,其中3例合并FLT3-ITD/TKD突变,均未缓解,另1例合并K/NRAS突变,为复发难治患者,达CR/CRi;K/NRAS突变4例中,2例合并FLT3-ITD/TKD突变,其中1例未缓解、1例PR,另外2例达CR/CRi,ORR为75.0%(3/4)。12例复发难治患者中,至随访结束,6例死亡,中位OS时间2.6个月(1~8个月),其中4例疾病进展,2例疾病复发;生存的6例患者病情稳定。18例患者均发生≥3级血液学不良反应,非血液学不良反应包括肺部感染、恶心、呕吐、腹泻等。结论 Ven+AZA治疗初治及复发难治AML患者可获得较高的治疗反应率,不良反应可耐受,但对于伴FLT3-ITD/TKD突变的AML患者疗效不佳。

Objective To explore the clinical short-term efficacy of venetoclax(Ven)combined with azacitidine(AZA)in treatment of newly treated and relapsed/refractory patients with acute myeloid leukemia(AML).Methods The data of 18 newly treated and relapsed/refractory patients with AML who received Ven+AZA treatment in Suzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine from April 2020 to June 2022 were retrospectively analyzed.The complete remission or complete remission with incomplete recovery of blood cell count(CR/CRi)and objective remission rate(ORR)[calculated as CR/CRi+partial remission(PR)]were analyzed in newly treated and relapsed/refractory patients or patients with different gene mutations.The patients were followed up until June 30,2022,and the overall survival(OS)of relapsed/refractory patients was analyzed.The occurrence of adverse reactions was summarized.Results The median age of the 18 patients was 58 years old(23-81 years old),8 were males and 10 were females;6 were newly treated and 12 were relapsed/refractory;the median follow-up time was 3 months(1-15 months).In 6 newly treated patients,after the first cycle of Ven+AZA,5 cases achieved CR/CRi,and the ORR was 83.3%(5/6).In 12 relapsed/refractory patients,after the first cycle of Ven+AZA,5 cases achieved CR/CRi,3 achieved PR,and the ORR was 66.7%(8/12).Among the 18 patients,7 cases had FLT3-ITD/TKD mutation,after the first cycle of Ven+AZA,1 case achieved CR/CRi,1 case achieved PR,and the ORR was 28.6%(2/7);3 cases had NPM1 mutation combined with FLT3-ITD/TKD mutation,1 case achieved CR/CRi,and the ORR was 33.3%(1/3);4 cases had IDH1/2 mutation,and 3 cases of them combined with FLT3-ITD/TKD mutation,all of which were non-remission,and the other 1 relapsed/refractory patient combined with K/NRAS mutation achieved CR/CRi;among the 4 cases with K/NRAS mutation,2 cases combined with FLT3-ITD/TKD mutation,including 1 case of NR and 1 case of PR,and the other 2 cases achieved CR/CRi,the ORR was 75.0%(3/4).Of the 12 relapsed/refractory patients,6 died by the end of follow-up,with a median OS time of 2.6 months(1-8 months),including 4 cases of disease progression and 2 cases of disease relapse;the 6 surviving patients had stable disease.All the 18 patients had≥grade 3 hematologic adverse reactions,and non-hematologic adverse reactions included lung infection,nausea,vomiting and diarrhea.Conclusions Ven+AZA treatment for newly treated and relapsed/refractory AML patients results in a high response rate with tolerable adverse reactions,but it is not effective in AML patients with FLT3-ITD/TKD mutation.