目的：观察以阿扎胞苷联合venetoclax治疗新诊断老年急性髓系白血病（acute myeloid leukemia,AML）的临床疗效及安全性。方法：回顾性分析上海交通大学医学院附属瑞金医院2018年3月至2020年9月收治的14例新诊断初治、不适合强化疗老年AML患者,阿扎胞苷75 mg/m²第1~7天（d1~7） 皮下注射,venetoclax每日口服400 mg d1~28,28 d为1个疗程（首次疗程venetoclax 100 mg d1、200 mg d2、400 mg d3~28口服）。临床观察主要终点为复合完全缓解率[完全缓解（complete remission,CR）+CR伴血细胞不完全恢复（CR with incomplete blood count recovery,CRi）]、总反应率（overall response rate,ORR）、首次到达反应时间及反应持续时间（duration of response,DOR）,次要终点为总生存（overall survival,OS）期及药物安全性。结果：14例老年AML患者中位随访时间为12.5（2.0~24.0）个月,CR+CRi率为71%,ORR为79%,中位首次到达反应时间为1.1（1.0~2.1）个月,中位DOR为16.0个月[95%置信区间（confidence interval,CI）: 4.0~未达到(not reached, NR)],中位OS期为14.0个月（95%CI: 2.0~NR）;在细胞遗传学中高危的12例患者中,共8例（67%）获CR+CRi,中位DOR为9.0个月（95%CI: 2.0~NR）,中位OS期为11.0个月（95%CI: 2.0~NR）;在CR+CRi的10例患者中,至少1次达到微小残留病灶（minimal residual disease, MRD）<0.01%有8例（80%）,其中位DOR为17.0个月（95%CI: 4.0~NR）,中位OS期未达到（95%CI: 6.0~NR）。所有患者都发生血液系统不同程度的细胞减少,最常见的3级以上不良反应为粒细胞减少（100%）,粒细胞减少伴发热6例（43%）,血小板减少7例（50%）,贫血5例（36%）;血液系统以外常见的主要为胃肠道反应,皆为可控的1~2级;1例发生肿瘤溶解综合征;大部分患者耐受。结论：初步结果表明,阿扎胞苷联合venetoclax有效且安全,为不适合强化疗的初治老年AML患者提供了治疗选择。

Objective To observe the clinical efficacy and safety of azacitidine combined with venetoclax in the treatment of newly diagnosed, elderly patients with acute myeloid leukemia (AML). Methods Fourteen elderly patients admitted in Ruijin Hospital from March 2018 to September 2020, who were newly diagnosed with AML and not suitable for intensive chemotherapy, were enrolled and a retrospective analysis was conducted. All patients received 75 mg/m² azacitidine subcutaneously from day 1 to day 7, and venetoclax orally once a day, total 28 d(the first cause of venetoclax treatment: 100 mg in day 1, 200 mg in day 2, 400 mg from day 3 to day 28). The primary end points were composite complete remission rate (CR+CRi), overall response rate (ORR), time to first response(CR/CRi ) and duration of response (DOR), and the secondary end points were overall survival(OS) and safety. Results The median follow-up time was 12.5 (2.0-24.0) months, the composite complete remission rate (CR+CRi) was 71%, ORR was 79%, the median time to first response was 1.1 (1.0-2.1) months, the median DOR was 16.0 months [95% confidence interval (CI): 4.0-not reached(NR)], and the median OS was 14.0 months (95% CI: 4.0-NR). Among 12 patients with median and high danger of poor cytogenetics, 8 patients (67%) achieved CR+CRi, the median DOR was 9.0 months (95% CI: 2.0-NR), and the median OS was 11.0 months (95% CI: 2.0-NR). Among 10 patients with CR + CRi, 8 patients(80%) achieved MRD<0.01% at least in one assessment, the median DOR was 17.0 months (95% CI: 4.0-NR) and the median OS did not reach (95% CI: 6.0-NR）。All patients showed cytopenia in different degree, including neutropenia of grade 3 or above (100%), thrombocytopenia (7 cases, 50%), febrile neutropenia (6 cases, 43%) and anemia (5 cases, 36%). The other common events occurred in gastrointestinal tract, which were all controllable response of grade 1-2. One patient showed tumor lysis syndrome. Most patients were tolerant to treatment. Conclusions The preliminary results show that the combination therapy of azacitidine and venetoclax is effective and safe, which provides a treatment option for elderly, untreated AML patients who are not suitable for intensive chemotherapy.