Issa Ghayas C, Aldoss Ibrahim, Thirman Michael J, DiPersio John, Arellano Martha, Blachly James S, Mannis Gabriel N, Perl Alexander, Dickens David S, McMahon Christine M, Traer Elie, Zwaan C Michel, Grove Carolyn S, Stone Richard, Shami Paul J, Mantzaris Ioannis, Greenwood Matthew, Shukla Neerav, Cuglievan Branko, Kovacsovics Tibor, Gu Yu, Bagley Rebecca G, Madigan Kate, Chudnovsky Yakov, Nguyen Huy Van, McNeer Nicole, Stein Eytan M
Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA.
J Clin Oncol. 2025 Jan;43(1):75-84. doi: 10.1200/JCO.24.00826. Epub 2024 Aug 9.
Revumenib, an oral, small molecule inhibitor of the menin-lysine methyltransferase 2A (KMT2A) interaction, showed promising efficacy and safety in a phase I study of heavily pretreated patients with -rearranged () acute leukemia. Here, we evaluated the activity of revumenib in individuals with relapsed/refractory (R/R) acute leukemia.
AUGMENT-101 is a phase I/II, open-label, dose-escalation and expansion study of revumenib conducted across 22 clinical sites in five countries (ClinicalTrials.gov identifier: NCT04065399). We report results from the phase II, registration-enabling portion. Individuals age ≥30 days with R/R acute leukemia or with AML and nucleophosmin 1 () mutation were enrolled. Revumenib was administered once every 12 hours, at 163 mg (95 mg/m if weight <40 kg) with a strong cytochrome P450 inhibitor, in 28-day cycles. The primary end points were the rate of complete remission (CR) or CR with partial hematologic recovery (CR + CRh) and safety. At a prespecified interim analysis, safety was assessed in all treated patients; efficacy was assessed in those with centrally confirmed . The separate cohort of the trial is ongoing.
From October 1, 2021, to July 24, 2023, N = 94 patients (median [range] age, 37 [1.3-75] years) were treated. Grade ≥3 adverse events included febrile neutropenia (37.2%), differentiation syndrome (16.0%), and QTc prolongation (13.8%). In the efficacy-evaluable patients (n = 57), the CR + CRh rate was 22.8% (95% CI, 12.7 to 35.8), exceeding the null hypothesis of 10% ( = .0036). Overall response rate was 63.2% (95% CI, 49.3 to 75.6), with 15 of 22 patients (68.2%) having no detectable residual disease.
Revumenib led to high remission rates with a predictable safety profile in R/R acute leukemia. To our knowledge, this trial represents the largest evaluation of a targeted therapy for these patients.
瑞武尼布是一种口服小分子抑制剂，可抑制Menin-赖氨酸甲基转移酶2A（KMT2A）相互作用，在一项针对经过大量预处理的KMT2A重排（KMT2A-r）急性白血病患者的I期研究中显示出有前景的疗效和安全性。在此，我们评估了瑞武尼布在复发/难治性（R/R）KMT2A-r急性白血病患者中的活性。
AUGMENT-101是一项在五个国家的22个临床地点进行的瑞武尼布的I/II期、开放标签、剂量递增和扩展研究（ClinicalTrials.gov标识符：NCT04065399）。我们报告II期注册启用部分的结果。年龄≥30天的R/R KMT2A-r急性白血病或急性髓系白血病（AML）伴核磷蛋白1（NPM1）突变的患者入组。瑞武尼布每12小时给药一次，剂量为163毫克（如果体重<40千克则为95毫克/平方米），同时使用一种强效细胞色素P450抑制剂，每28天为一个周期。主要终点是完全缓解（CR）率或伴有部分血液学恢复的CR（CR + CRh）率以及安全性。在预先指定的中期分析中，对所有接受治疗的患者进行安全性评估；对经中心确认的患者进行疗效评估。该试验的单独NPM1队列正在进行中。
从2021年10月1日至2023年7月24日，共治疗了N = 94例患者（中位[范围]年龄，37[1.3 - 75]岁）。≥3级不良事件包括发热性中性粒细胞减少（37.2%）、分化综合征（16.0%）和QTc延长（13.8%）。在可评估疗效的患者（n = 57）中，CR + CRh率为22.8%（95%CI，12.7至35.8），超过了10%的零假设（P = .0036）。总缓解率为63.2%（95%CI，49.3至75.6），22例患者中有15例（68.2%）检测不到残留疾病。
瑞武尼布在R/R KMT2A-r急性白血病中导致高缓解率，且安全性可预测。据我们所知，该试验是对这些患者靶向治疗的最大规模评估。
Zotero 插件
