目的：总结35例不耐受强化疗的初治老年急性髓系白血病（acute myeloid leukemia, AML）的临床特点，评估维奈克拉（venetoclax，VEN）联合阿扎胞苷（azacytidine，AZA）的疗效及安全性。方法：纳入本院2021年2月至2022年3月间诊断的35例不耐受强化疗的初治老年AML患者，接受VEN+AZA诱导治疗，回顾性分析其临床特征、VEN+AZA诱导的缓解情况及治疗安全性。结果：患者中位年龄68岁，继发AML 9例。所有患者均完成骨髓细胞遗传学及分子生物学评估，其中低危患者10例，中危12例，高危13例。常见的基因突变为DNA甲基转移酶3A（DNA methyltransferase 3A，DNMT3A）（11例）、异柠檬酸脱氢酶1/2（isocitrate dehydrogenase 1/2，IDH1/2）（11例）、TET癌基因家族成员2（ten-eleven translocation 2，TET2）（9例）、核仁磷酸蛋白1(nucleophosmin 1，NPM1）（8例）、Fms-样酪氨酸激酶3-内部串联重复（Fms-related tyrosine kinase 3-internal tandem duplication，FLT3-ITD）（6例）。总完全缓解（complete remission，CR）率65.7%（23例），NPM1、FLT3-ITD、IDH1/2突变患者CR率分别为87.5%、66.7%、72.7%。CR患者中总微小残留病变（minimal residual disease，MRD）阴性率73.9%。中位随访时间10.1个月，中位无事件生存（event-free survival，EFS）期11.3个月。缓解患者中，相比于MRD阳性患者，MRD阴性患者EFS及总生存（overall survival, OS）期更长（P<0.05）。早期死亡率5.7%，治疗过程中最常见的不良反应为血液学毒性（3~4级中性粒细胞减少31.4％、3~4级血小板减少25.7％、中性粒细胞减少性发热48.6%）及肺部感染（17.1%）。结论：VEN+AZA在不耐受强化疗的初治老年AML中治疗的总缓解率较高。NPM1突变可能提示更高缓解率。MRD转阴患者EFS期及OS期较MRD阳性患者延长，死亡风险下降。VEN+AZA是目前不能耐受强化疗的初治老年AML重要的治疗选择之一。

Objective To investigate the clinical characteristics of 35 elderly patients with acute myeloid leukemia (AML) who were newly treated and intolerant to intensive chemotherapy and evaluate treatment efficacy and safety of venetoclax combined with azacytidine (VEN+AZA). Methods Between February 2021 and March 2022, 35 AML elderly patients who were intolerant to intensive therapy were enrolled in the study. They received VEN+AZA induction therapy. The disease characteristics, VEN+AZA induced remission and treatment safety were retrospectively analyzed and reported. Results The median age of enrolled patients was 68 year old, and there were 9 cases diagnosed with secondary AML. All patients completed bone marrow cytogenetic and molecular biology evaluation and were stratified by European LeukemiaNet (ELN) genetic risk classification. Thirty-five patients were classified as low risk group (10 of 35 cases), intermediate risk group (12 of 35 cases) and high risk group (13 of 35 cases). Common genetic mutations included DNA methyltransferase 3A (DNMT3A) (n=11), isocitrate dehydrogenase (IDH) 1/2 (n=11), ten-eleven translocation 2 (TET2) (n=9), NPM1 (n=8) and Fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) (n=6). The overall complete remission (CR) rate of treatment was 65.7% (n=23), and the CR rate of patients with mutation of NPM1, FLT3-ITD, IDH1/2 were 87.5%, 66.7% and 72.7%, respectively. The total negative rate of minimal residual disease (MRD) among CR patients was 73.9%, the median follow-up time was 10.1 months and median event-free survival (EFS) was 11.3 months. Among remission patients, MRD-negative patients had longer EFS and overall survival than MRD-positive patients（P<0.05）. The early mortality rate was 5.7%. The most common adverse reaction during treatment was hematological toxicity (treatment-induced grade 3-4 neutropenia 31.4%, grade 3-4 thrombocytopenia 25.7%, febrile neutropenia 48.6%) and pulmonary infection (17.1%). Conclusions Our results showed that VEN+AZA has a higher overall response rate in newly treatment elderly AML who were intolerant to intensive chemotherapy, which was similar with the clinical trial results. NPM1 mutation might indicate higher CR rate. The EFS and OS of MRD-negative patients were longer than those of MRD-positive patients, and the risk of death was reduced. In summary, VEN+AZA regime was currently one of the most promising strategies for newly treated elderly AML who couldn’t tolerate intensive chemotherapy.