Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lancet Haematol. 2024 Apr;11(4):e287-e298. doi: 10.1016/S2352-3026(24)00034-6.
Patients with acute myeloid leukaemia have high rates of relapse, especially if they are unable to complete standard consolidation strategies or allogeneic haematopoietic stem-cell transplantation (HSCT). The phase 3 QUAZAR AML-001 study showed an overall survival benefit with oral azacitidine maintenance. The BCL2 inhibitor venetoclax is highly active in acute myeloid leukaemia and synergistic with azacitidine. We aimed to evaluate the efficacy and safety of low dose azacitidine plus venetoclax as maintenance therapy in acute myeloid leukaemia.
We performed a single-centre, single-arm, phase 2 study at the University of Texas MD Anderson Cancer Center in the USA. Eligible patients were adults (aged ≥18 years) with a WHO 2016 diagnosis of acute myeloid leukaemia in complete remission or complete remission with incomplete blood count recovery following intensive or low-intensity induction and not immediately eligible for HSCT. Eastern Cooperative Oncology Group performance status had to be 3 or less. Patients were assigned to maintenance therapy with azacitidine 50 mg/m intravenously or subcutaneously for 5 days and venetoclax 400 mg orally for 7 days or 14 days. The primary outcome was relapse-free survival. The study was closed early due to slow accrual. All patients were included in the efficacy and safety analyses. This trial is registered with ClinicalTrials.gov (NCT04062266).
Between Sept 26, 2019, and Oct 26, 2022, 35 patients were enrolled, of whom 25 (71%) were assigned to cohort 1 following intensive induction and ten (29%) to cohort 2 following low-intensity induction. Of 35 patients, 18 (51%) were male and 17 (49%) were female. The median age was 55 years (IQR 41-62). The median number of cycles given was 9 (IQR 2-22) and median follow-up time was 23·3 months (IQR 9·0-30·0). The median relapse-free survival was not reached (95% CI 20·2 to not calculable) in the full cohort, not reached (29·1 to not calculable) in cohort 1, and 30·3 months (16·5 to not calculable) in cohort 2. The 2-year relapse-free survival was 65% (95% CI 50-85) in the full cohort, 71% (53-94) in cohort 1, and 52% (27-100) in cohort 2. The most common grade 3-4 treatment-emergent adverse events were thrombocytopenia (n=6), lung infection (n=4), leukopenia (n=4), and neutropenia (n=3). No deaths occurred during maintenance therapy.
Low dose azacitidine plus venetoclax is a feasible maintenance strategy in acute myeloid leukaemia following intensive and low-intensity induction.
University of Texas MD Anderson Cancer Center, MDS/AML Moon Shot, Genentech.
急性髓系白血病患者的复发率较高，尤其是那些无法完成标准巩固治疗策略或异体造血干细胞移植（HSCT）的患者。3 期 QUAZAR AML-001 研究显示，口服阿扎胞苷维持治疗可带来总生存获益。BCL2 抑制剂维奈妥拉在急性髓系白血病中具有高度活性，与阿扎胞苷具有协同作用。我们旨在评估低剂量阿扎胞苷联合维奈妥拉作为急性髓系白血病维持治疗的疗效和安全性。
我们在美国德克萨斯大学 MD 安德森癌症中心进行了一项单中心、单臂、2 期研究。符合条件的患者为年龄≥18 岁的成年人，根据世界卫生组织 2016 年标准诊断为完全缓解或强化或低强度诱导后不完全血液计数恢复的完全缓解期急性髓系白血病，且不立即适合进行 HSCT。东部肿瘤协作组体能状态必须为 3 或更低。患者被分配接受阿扎胞苷 50mg/m 静脉或皮下注射 5 天和维奈妥拉 400mg 口服 7 天或 14 天的维持治疗。主要终点是无复发生存期。由于入组缓慢，该研究提前关闭。所有患者均纳入疗效和安全性分析。该试验在 ClinicalTrials.gov 注册（NCT04062266）。
在 2019 年 9 月 26 日至 2022 年 10 月 26 日期间，共纳入 35 例患者，其中 25 例（71%）在强化诱导后被分配到队列 1，10 例（29%）在低强度诱导后被分配到队列 2。35 例患者中，18 例（51%）为男性，17 例（49%）为女性。中位年龄为 55 岁（IQR 41-62）。中位周期数为 9（IQR 2-22），中位随访时间为 23.3 个月（IQR 9.0-30.0）。全队列的中位无复发生存期未达到（95%CI 20.2 至不可计算），队列 1 未达到（29.1 至不可计算），队列 2 为 30.3 个月（16.5 至不可计算）。全队列的 2 年无复发生存率为 65%（95%CI 50-85），队列 1 为 71%（53-94），队列 2 为 52%（27-100）。最常见的 3-4 级治疗相关不良事件为血小板减少症（n=6）、肺部感染（n=4）、白细胞减少症（n=4）和中性粒细胞减少症（n=3）。在维持治疗期间没有死亡发生。
低剂量阿扎胞苷联合维奈妥拉是强化和低强度诱导后急性髓系白血病的一种可行的维持治疗策略。
德克萨斯大学 MD 安德森癌症中心，MDS/AML 登月计划，罗氏。
