Arellano Martha L, Thirman Michael J, DiPersio John F, Heiblig Mael, Stein Eytan M, Schuh Andre C, Zucenka Andrius, De Botton Stéphane, Grove Carolyn S, Mannis Gabriel N, Papayannidis Cristina, Perl Alexander E, Issa Ghayas C, Aldoss Ibrahim, Bajel Ashish, Dickens David S, Kühn Michael W M, Mantzaris Ioannis, Raffoux Emmanuel, Traer Elie, Amitai Irina, Döhner Hartmut, Greco Corinna, Kovacsovics Tibor J, McMahon Christine M, Montesinos Pau, Pigneux Arnaud, Shami Paul J, Stone Richard M, Wolach Ofir, Harpel John G, Chudnovsky Yakov, Yu Li, Bagley Rebecca G, Smith Angela R, Blachly James S
Winship Cancer Institute of Emory University School of Medicine, United States.
The University of Chicago Medicine, United States.
Blood. 2025 May 7. doi: 10.1182/blood.2025028357.
The prognosis for relapsed or refractory (R/R) nucleophosmin 1-mutated (NPM1m) acute myeloid leukemia (AML) is poor and represents an urgent unmet medical need. Revumenib, a potent, selective menin inhibitor, was recently approved for the treatment of R/R acute leukemia with a KMT2A translocation in patients aged ≥1 year based on results from the phase 1/2 AUGMENT-101 study. Here we present results from patients with R/R NPM1m AML enrolled in the phase 2 portion of AUGMENT-101. Enrolled patients received revumenib with or without a strong CYP3A4 inhibitor every 12 hours in 28-day cycles. Primary endpoints were rate of complete remission (CR) or CR with partial hematologic recovery (CRh; CR+CRh), and safety and tolerability. Secondary endpoints included overall response rate (ORR) and duration of response. As of September 18, 2024, 84 patients received ≥1 dose of revumenib. Median age was 63 years; 1 patient was aged <18 years. The protocol-defined efficacy-evaluable population for the primary analysis included 64 adult patients (≥3 prior lines of therapy, 35.9%; prior venetoclax, 75.0%). The CR+CRh rate was 23.4% (1-sided P=.0014); the ORR was 46.9%. Median duration of CR+CRh was 4.7 months. Five of 30 responders (16.7%) proceeded to hematopoietic stem cell transplant (HSCT); 3 resumed revumenib after HSCT. Treatment-related adverse events led to treatment discontinuation in 4 patients (4.8%). Revumenib demonstrated clinically meaningful responses in this heavily pretreated, older population with NPM1m AML, including remissions that enabled HSCT. The safety profile of revumenib was consistent with previously reported results. This trial was registered at www.clinicaltrials.gov as NCT04065399.
复发或难治性（R/R）核磷蛋白1突变（NPM1m）急性髓系白血病（AML）的预后较差，是一种亟待满足的医疗需求。瑞武尼布是一种强效、选择性的Menin抑制剂，基于1/2期AUGMENT-101研究的结果，最近被批准用于治疗年龄≥1岁的伴有KMT2A易位的R/R急性白血病。在此，我们展示了参与AUGMENT-101 2期研究的R/R NPM1m AML患者的结果。入组患者每12小时接受一次瑞武尼布治疗，有或没有强效CYP3A4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（CRh；CR+CRh），以及安全性和耐受性。次要终点包括总缓解率（ORR）和缓解持续时间。截至2024年9月18日，84例患者接受了≥1剂瑞武尼布治疗。中位年龄为63岁；1例患者年龄<18岁。用于主要分析的方案定义的疗效可评估人群包括64例成年患者（≥3线既往治疗，35.9%；既往使用维奈克拉，75.0%）。CR+CRh率为23.4%（单侧P=0.0014）；ORR为46.9%。CR+CRh的中位持续时间为4.7个月。30例缓解者中有5例（16.7%）进行了造血干细胞移植（HSCT）；3例在HSCT后恢复使用瑞武尼布。治疗相关不良事件导致4例患者（4.8%）停药。瑞武尼布在这个经过大量预处理的老年NPM1m AML患者群体中显示出具有临床意义的缓解，包括使HSCT成为可能的缓解。瑞武尼布的安全性与先前报告的结果一致。该试验已在www.clinicaltrials.gov上注册，注册号为NCT04065399。
