Most older patients with acute myeloid leukemia (AML) who attain morphologic remission with intensive chemotherapy (IC) will eventually relapse and post-relapse prognosis is dismal. In the pivotal QUAZAR AML-001 trial, oral azacitidine maintenance therapy significantly prolonged overall survival by 9.9 months (P < 0.001) and relapse-free survival by 5.3 months (P < 0.001) compared with placebo in patients with AML in first remission after IC who were not candidates for transplant. Currently, the QUAZAR AML-001 trial provides the most comprehensive safety information associated with oral azacitidine maintenance therapy. Reviewed here are common adverse events (AEs) during oral azacitidine treatment in QUAZAR AML-001, and practical recommendations for AE management based on guidance from international cancer consortiums, regulatory authorities, and the authors’ clinical experience treating patients in the trial. QUAZAR AML-001 is an international, placebo-controlled randomized phase 3 study. Patients aged ≥ 55 years with AML and intermediate- or poor-risk cytogenetics at diagnosis, who had attained first complete remission (CR) or CR with incomplete blood count recovery (CRi) within 4 months before study entry, were randomized 1:1 to receive oral azacitidine 300 mg or placebo once-daily for 14 days in repeated 28-day cycles. Safety was assessed in all patients who received ≥ 1 dose of study drug. A total of 469 patients received oral azacitidine (n = 236) or placebo (n = 233). Median age was 68 years. Patients received a median of 12 (range 1–80) oral azacitidine treatment cycles or 6 (1–73) placebo cycles. Gastrointestinal AEs were common and typically low-grade. The most frequent grade 3–4 AEs during oral azacitidine therapy were hematologic events. AEs infrequently required permanent discontinuation of oral azacitidine (13%), suggesting they were effectively managed with use of concomitant medications and oral azacitidine dosing modifications. Oral azacitidine maintenance had a generally favorable safety profile. Prophylaxis with antiemetic agents, and blood count monitoring every other week, are recommended for at least the first 2 oral azacitidine treatment cycles, and as needed thereafter. Awareness of the type, onset, and duration of common AEs, and implementation of effective AE management, may maximize treatment adherence and optimize the survival benefits of oral azacitidine AML remission maintenance therapy. Trial registration This trial is registered on clinicaltrials.gov: NCT01757535 as of December 2012.

中文翻译：

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接受口服阿扎胞苷缓解的急性髓系白血病患者不良事件的管理：来自 3 期随机 QUAZAR AML-001 试验的经验

大多数通过强化化疗（IC）获得形态学缓解的老年急性髓系白血病（AML）患者最终会复发，并且复发后预后不佳。在关键的 QUAZAR AML-001 试验中，对于 IC 后首次缓解的 AML 患者，口服阿扎胞苷维持治疗与安慰剂相比显着延长了 9.9 个月的总生存期（P < 0.001）和 5.3 个月的无复发生存期（P < 0.001）谁不是移植的候选人。目前，QUAZAR AML-001 试验提供了与口服阿扎胞苷维持治疗相关的最全面的安全信息。此处审查了 QUAZAR AML-001 中口服阿扎胞苷治疗期间的常见不良事件 (AE)，以及基于国际癌症联盟、监管机构、以及作者在试验中治疗患者的临床经验。QUAZAR AML-001 是一项国际、安慰剂对照的随机 3 期研究。年龄 ≥ 55 岁且诊断时为中危或低危细胞遗传学的 AML 患者，在研究开始前 4 个月内获得首次完全缓解 (CR) 或血细胞计数不完全恢复 (CRi) 的 CR，按 1:1 随机分组至每天一次口服阿扎胞苷 300 毫克或安慰剂，持续 14 天，重复 28 天周期。在接受≥ 1 剂研究药物的所有患者中评估安全性。共有 469 名患者接受了口服阿扎胞苷（n = 236）或安慰剂（n = 233）。中位年龄为 68 岁。患者接受中位数为 12 个（范围 1-80）个口服阿扎胞苷治疗周期或 6 个（1-73）个安慰剂周期。胃肠道 AE 很常见，而且通常是低级别的。口服阿扎胞苷治疗期间最常见的 3-4 级 AE 是血液学事件。AE 很少需要永久停止口服阿扎胞苷 (13%)，这表明它们可以通过使用伴随药物和口服阿扎胞苷剂量调整得到有效控制。口服阿扎胞苷维持治疗具有普遍良好的安全性。建议至少在前 2 个口服阿扎胞苷治疗周期内使用止吐药进行预防，并每隔一周监测一次血细胞计数，并在此后根据需要进行。了解常见 AE 的类型、发作和持续时间，并实施有效的 AE 管理，可以最大限度地提高治疗依从性并优化口服阿扎胞苷 AML 缓解维持治疗的生存获益。试验注册 该试验在clinicaltrials.gov 上注册：