Departamento de Hematologia, Hospital Universitari i Politècnic La Fe, València, Spain.
CIBERONC, Instituto Carlos III, Madrid, Spain.
Future Oncol. 2020 May;16(13):807-815. doi: 10.2217/fon-2020-0044. Epub 2020 Mar 13.
Patients with refractory or relapsed acute myeloid leukemia (R/R AML) have a poor prognosis, with a high unmet medical need. Idasanutlin is a small-molecule inhibitor of MDM2, a negative regulator of tumor suppressor p53. By preventing the p53-MDM2 interaction, idasanutlin allows for p53 activation, particularly in patients with wild-type (WT) status. MIRROS (NCT02545283) is a randomized Phase III trial evaluating idasanutlin + cytarabine versus placebo + cytarabine in R/R AML. The primary end point is overall survival in the -WT population. Secondary end points include complete remission rate (cycle 1), overall remission rate (cycle 1) and event-free survival in the -WT population. MIRROS has an innovative design that integrates a stringent interim analysis for futility; continuation criteria were met in mid-2017 and accrual is ongoing. NCT02545283.
难治性或复发性急性髓系白血病（R/R AML）患者预后较差，未满足的医疗需求很高。Idasanutlin 是一种 MDM2 的小分子抑制剂，MDM2 是肿瘤抑制因子 p53 的负调节因子。通过防止 p53-MDM2 相互作用，idasanutlin 允许 p53 激活，特别是在野生型（WT）状态的患者中。MIRROS（NCT02545283）是一项随机 III 期试验，评估 idasanutlin + 阿糖胞苷与安慰剂 + 阿糖胞苷在 R/R AML 中的疗效。主要终点是 -WT 人群的总生存期。次要终点包括 -WT 人群的第 1 周期完全缓解率、第 1 周期总缓解率和无事件生存期。MIRROS 的设计具有创新性，它整合了一个严格的中期分析来判断无效性；在 2017 年年中达到了继续标准，目前正在继续入组。NCT02545283。
