[Efficacy of venetoclax combined azacitidine in newly diagnosed acute myeloid leukemia unfit for standard chemotherapy: a single center experience].

Objective: To investigate the effectiveness and safety of the VA regimen, which combines venetoclax with azacitidine in the treatment of patients with newly diagnosed acute myeloid leukemia (AML) who are not suitable candidates for conventional chemotherapy. Methods: In the Department of Hematology at the Second Hospital of Hebei Medical University, 66 AML patients who received venetoclax and azacitidine treatment from May 2020 to March 2022 were the subject of a retrospective study. The complete remission (CR) rate, cCR rate, ORR rate, MRD negative rate, the incidence of adverse events,1-year EFS, and OS were retrospectively analyzed. Patients subgroups with varying ages, ECOG scores, primary and secondary, risk stratifications, and gene mutation were compared for differences in efficacy and survival. Results: The median follow-up was 4.25 (0.9-19.9) months, and the median number of treatment courses was 2 (1-8) cycles. After the first cycle, the cCR rate was 78.8% , and the MRD negative rate was 51.9% . After prolonged treatment, the cCR rate was 81.8% and MRD negative rate was 66.7% . The median EFS and OS, respectively, were13.2 and 15.3 months. Secondary AML showed inferior efficacy and prognosis. IDH1/2 or NPM1 mutation groups had a significantly higher rate of CR than the control group (P<0.05) . The CR rate and MRD negative rate of patients with rebound thrombocytosis were significantly higher than those without rebound thrombocytosis (P<0.05) . Those who had epigenetic modification mutations (DNMT3, ASXL1, TET2) were more likely to benefit from ongoing therapy. The most common grade 3 and 4 adverse reactions were neutropenia, thrombocytopenia, and anemia. Conclusions: In real-world patients with newly diagnosed AML who are not candidates for standard chemotherapy, the VA regimen produces rapid deep remission. Primary AML patients, rebound thrombocytosis, IDH1/2, and NPM1 gene mutations are favorable factors for treatment benefit, and adverse reactions were tolerable.目的： 回顾性分析维奈克拉联合阿扎胞苷（venetoclax+ azacitidine，VA）治疗不适合标准化疗的新诊断急性髓系白血病（AML）患者的疗效和安全性。 方法： 收集河北医科大学第二医院自2020年5月至2022年3月收治的VA方案治疗的66例不适合标准化疗新诊断AML患者的临床资料，回顾性分析其完全缓解（CR）率、总反应率（ORR）、微小残留病（MRD）阴性率、无事件生存（EFS）率、总生存（OS）率及不良反应发生率。比较不同年龄、ECOG评分、原发与继发、预后分层和分子突变亚组患者的疗效和生存差异。 结果： 中位随访4.25（0.9~19.9）个月，中位疗程数2（1~8）个。1个疗程复合CR（cCR）率[CR+血液学未完全恢复的CR（CRi）率]和MRD阴性率分别为78.8%、51.9%，≥2个疗程的cCR率和MRD阴性率分别为81.8%、66.7%。中位EFS和OS时间分别为13.2、15.3个月。亚组分析显示，继发AML患者疗效及生存均差于原发AML患者，发生反弹性血小板增多患者疗效及生存显著优于无反弹性血小板增多患者（P值均<0.05）。IDH1/2突变及NPM1突变患者1个疗程CR率均显著高于无相应突变组，存在表观遗传学修饰相关DAT（DNMT3、ASXL1、TET2）突变的患者，≥2个疗程的持续治疗更可能获得最佳疗效。最常见的3~4级不良反应为中性粒细胞减少、血小板减少和贫血。 结论： 真实世界不适合标准化疗的新诊断AML患者应用VA方案可较快获得深层次缓解。原发AML、IDH1/2突变、NPM1突变及反弹性血小板增多是治疗获益的有利因素。不良反应可耐受。.