维奈克拉联合阿扎胞苷与地西他滨联合预激方案治疗老年复发急性髓系白血病的疗效及安全性比较的初步观察

Efficacy and safety of venetoclax combined with azacitidine versus CAG regimen combined with decitabine in elderly patients with relapsed acute myeloid leukemia

目的比较维奈克拉(venetoclax,VEN)联合阿扎胞苷(azacitidine,AZA)方案与地西他滨(decitabine/dacogen,DAC)联合预激方案治疗老年复发急性髓系白血病(acute myeloid leukemia,AML)的疗效及安全性。方法回顾性分析2018年1月至2020年8月苏州大学附属第一医院血液科收治的45例老年复发AML患者的临床资料,男性31例、女性14例,年龄60~80岁,中位年龄66岁,其中18例采用VEN+AZA方案治疗,27例采用DAC+预激方案治疗。比较两组患者的完全缓解率(complete remission,CR)、部分缓解率(partial remission,PR)、总有效率(overall response rate,ORR),不良反应发生率以及总体生存(overall survival,OS)。结果VEN+AZA组ORR为14/18,其中CR 11例、PR 3例;DAC+预激组ORR为37.0%(10/27),其中CR 8例、PR 2例,两组患者疗效差异有统计学意义(P=0.007)。在中高危组(P=0.013)或DNA甲基化突变(P=0.007)的患者中,VEN+AZA组治疗后的ORR明显高于DAC+预激组。患者的主要不良反应为骨髓抑制、感染、恶心呕吐、纳差、乏力,VEN+AZA组治疗后Ⅲ~Ⅳ级外周血白细胞(66.7%比100%,P=0.002)、血红蛋白(50.0%比92.6%,P=0.002)、血小板(72.2%比96.3%,P=0.031)及中性粒细胞(61.1%比92.6%,P=0.014)减少的发生率低于DAC+预激组。DAC+预激组Ⅲ~Ⅳ级感染(66.7%比33.3%,P=0.028)、Ⅲ~Ⅳ级恶心呕吐和纳差(40.7%比11.1%,P=0.032)和Ⅲ~Ⅳ级乏力(55.6%比11.1%,P=0.003)的发生率均高于VEN+AZA组。VEN+AZA组和DAC+预激组的1年OS率分别为42.9%和31.6%,两组患者间的OS率比较差异无统计学意义(P=0.150)。结论VEN+AZA方案治疗老年复发AML患者有较好的疗效和安全性。

Objective To compare the efficacy and safety of venetoclax(VEN)combined with azacitidine(AZA)versus CAG regimen combined with decitabine(DAC)in elderly patients with relapsed acute myeloid leukemia(AML).Methods From January 2018 to August 2020,the clinical data of forty-five elderly patients with relapse AML at the First Affiliated Hospital of Soochow University were retrospectively analyzed,including 31 males and 14 females.The median age was 66(60-80)years old.Eighteen patients were administrated with VEN and AZA,while the other 27 were in CAG with DAC.The complete remission(CR)rate,partial remission(PR)rate,total remission rate(ORR),adverse events and overall survival(OS)were compared between the two groups.Results At the end of the treatment,the ORR in VEN with AZA group was 77.8%(14/18);including 11 CR and 3 PR.In CAG with DAC group,the ORR was 37.0%(10/27);including 8 CR and 2 PR(P=0.007).Subgroup analysis suggested that VEN with AZA had a higher ORR in patients stratified as intermediate and poor-risk(P=0.013)or with DNA methylation mutations(P=0.007).Main adverse events in both groups were bone marrow suppression,infections,nausea and vomiting,anorexia and fatigue.GradeⅢ-Ⅳcytopenia developed in lower incidence of VEN with AZA group,such as leukopenia(66.7%vs.100%,P=0.002),anemia(50.0%vs.92.6%,P=0.002),thrombocytopenia(72.2%vs.96.3%,P=0.031)and neutropenia(61.1%vs.92.6%,P=0.014).In addition,less gradeⅢ-Ⅳinfections occurred in VEN with AZA group(66.7%vs.33.3%,P=0.028),as well as gradeⅢ-Ⅳgastrointestinal events(40.7%vs.11.1%,P=0.032),gradeⅢ-Ⅳfatigue(55.6%vs.11.1%,P=0.003)compared with CAG with DAC group.The 1-year OS in VEN with AZA group versus CAG with DAC group was 42.9%and 31.6%respectively(P=0.150).Conclusion VEN combined with AZA proves favorable efficacy and tolerablity in elderly patients with relapsed AML.