The outcome of relapsed/refractory (R/R) acute myeloid leukemia (AML) remains extremely poor. Venetoclax (VEN)-based regimens have shown promise in treating R/R AML. This phase 2 study aimed to systematically evaluate the efficacy and safety of the VAA regimen (VEN plus Cytarabine and Azacitidine) in R/R AML patients. Thirty R/R AML patients were enrolled. The study adopted a stepwise ramp-up of VEN dosing, starting with 100 mg on day 1, escalating to 200 mg on day 2, and reaching 400 mg from day 3 to day 9. Cytarabine (10 mg/m, q12h) was administered intravenously twice daily from days 1 to 10, and Azacitidine (75 mg/m) was administered via subcutaneous injection once daily from days 1–7. The primary efficacy endpoint was the composite complete remission rate (CRc), including complete response (CR) and complete response with incomplete blood count recovery (CRi). Secondary endpoints included overall survival (OS), duration of response (DOR), and safety analysis. The CRc rate was 63.3% (19/30), with CR in 36.7% of patients and CRi in 26.7%. Notably, 14 (73.7%) of 19 patients achieving CRc showed undetectable measurable residual disease by flow cytometry. With a median follow-up of 10.7 months, the median OS had not been reached, and the median DOR was 18.3 months. The most common grade 3–4 adverse events (AEs) were neutropenia (100%), anemia (96.7%), thrombocytopenia (90.0%), and leukopenia (90.0%). Infections, with pneumonia being the most prevalent (43.3%), were observed, including one fatal case of Pseudomonas aeruginosa septicemia. There were no treatment-related deaths. The VAA regimen is an effective and safe option for patients with R/R AML, demonstrating a high CRc rate and manageable safety profile.

中文翻译：

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Venetoclax 联合阿糖胞苷和阿扎胞苷治疗复发/难治性 AML：一项开放标签、单臂、2 期研究

复发/难治性（R/R）急性髓系白血病（AML）的结果仍然极差。基于 Venetoclax (VEN) 的治疗方案在治疗 R/R AML 方面已显示出前景。这项 2 期研究旨在系统评估 VAA 方案（VEN 加阿糖胞苷和阿扎胞苷）在 R/R AML 患者中的疗效和安全性。招募了 30 名 R/R AML 患者。该研究采用逐步增加 VEN 剂量的方式，从第 1 天 100 mg 开始，第 2 天逐步增加到 200 mg，第 3 天到第 9 天达到 400 mg。阿糖胞苷（10 mg/m，每 12 小时一次）给药从第 1 天到第 10 天，每天两次静脉注射，从第 1 天到第 7 天，每天一次皮下注射阿扎胞苷 (75 mg/m)。主要疗效终点是复合完全缓解率（CRc），包括完全缓解（CR）和完全缓解伴不完全血细胞计数恢复（CRi）。次要终点包括总生存期 (OS)、缓解持续时间 (DOR) 和安全性分析。 CRc 率为 63.3%（19/30），其中 CR 率为 36.7%，CRi 率为 26.7%。值得注意的是，19 名达到 CRc 的患者中有 14 名（73.7%）显示出流式细胞术无法检测到的残留疾病。中位随访时间为 10.7 个月，中位 OS 尚未达到，中位 DOR 为 18.3 个月。最常见的 3-4 级不良事件 (AE) 为中性粒细胞减少症 (100%)、贫血 (96.7%)、血小板减少症 (90.0%) 和白细胞减少症 (90.0%)。观察到感染，其中肺炎最为常见（43.3%），其中包括一例铜绿假单胞菌败血症致死病例。没有出现与治疗相关的死亡。 VAA 方案对于 R/R AML 患者来说是一种有效且安全的选择，显示出高 CRc 率和可控的安全性。