Venetoclax+阿扎胞苷是治疗新诊断的急性髓系白血病（AML）患者标准，它适用于不能使用强化化疗的患者。努力优化此疗法是必要的。我们设计了一项临床试验以探讨两个假设：1）更高剂量的Venetoclax具有耐受性并更有效，2）在深度缓解后可停用阿扎胞苷。共有42名新诊断的AML患者入选了这项调查人员发起的高剂量停用阿扎胞苷+Venetoclax（HiDDAV）研究。患者接受1-3个Venetoclax 600mg每日与阿扎胞苷的“诱导”周期。响应者接受MRD阳性或阴性的“维持”阶段：阿扎胞苷与400mg Venetoclax或仅400mg Venetoclax。HiDDAV的毒性配置文件类似于400mg Venetoclax。总体响应率为66.7％；响应持续时间（DOR），无事件生存期（EFS）和总生存期分别为12.9，7.8和9.8个月。流式细胞术测得的MRD阴性率为64.3％，同时使用液滴数码PCR测量时为25.0％。通过流式细胞术测得的MRD阴性患者的DOR和EFS有所改善；更严格的MRD阴性测量指标与改善OS，DOR或EFS无关。使用MRD指导阿扎胞苷停止治疗未能导致比不使用MRD指导停止治疗的患者的DOR，EFS或OS有所改善。在这种研究设计的情况下，与阿扎胞苷一起的Venetoclax剂量> 400mg可以耐受，但与明显的临床改善不相关，MRD可能无法帮助推荐停用阿扎胞苷。需要其他策略来优化，并为一些患者减弱Venetoclax+阿扎胞苷方案。

Venetoclax+azacitidine is the standard of care for newly-diagnosed patients with acute myeloid leukemia (AML) for whom intensive chemotherapy is inappropriate. Efforts to optimize this regimen are necessary. We designed a clinical trial to investigate two hypotheses: 1)Higher doses of venetoclax are tolerable and more effective, and 2)Azacitidine can be discontinued after deep remissions. Forty-two newly-diagnosed AML patients were enrolled in the investigator-initiated High Dose Discontinuation Azacitidine + Venetoclax (HiDDAV) Study. Patients received 1-3 "induction" cycles of venetoclax 600mg daily with azacitidine. Responders received MRD-positive or negative "maintenance" arms: azacitidine with 400mg venetoclax or 400mg venetoclax alone, respectively. The toxicity profile of HiDDAV was similar to 400mg venetoclax. The overall response rate was 66.7%; the duration of response (DOR), event-free survival (EFS) and overall survival were 12.9, 7.8 and 9.8 months, respectively. The MRD-negativity rate was 64.3% by flow cytometry and 25.0% when also measured by droplet digital PCR. MRD-negative patients by flow cytometry had improved DOR and EFS; more stringent measures of MRD-negativity were not associated with improved OS, DOR or EFS. Using MRD to guide azacitidine discontinuation did not lead to improved DOR, EFS or OS compared to patients who discontinued azacitidine without MRD guidance. Within the context of this study design, venetoclax doses >400mg with azacitidine were well tolerated but not associated with discernible clinical improvement, and MRD may not assist in recommendations to discontinue azacitidine. Other strategies to optimize, and for some patients, de-intensify, venetoclax+azacitidine regimens are needed.