Menin inhibition with revumenib for NPM1 -mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study

作者：Martha Lucia Arellano, Michael J. Thirman, John F. DiPersio, Maël Heiblig, Eytan M. Stein, Andre C. Schuh, Andrius Žučenka, Stéphane de Botton, Carolyn S. Grove, Gabriel N. Mannis, Cristina Papayannidis, Alexander E. Perl, Ghayas C. Issa, Ibrahim Taha Aldoss, Ashish R. Bajel, David S. Dickens, Michael W.M. Kühn, Ioannis Mantzaris, Emmanuel Raffoux, Elie Traer, Irina Amitai, Hartmut Döhner, Corinna Greco, Tibor J. Kovacsovics, Christine M. McMahon, Pau Montesinos, Arnaud Pigneux, Paul J. Shami, Richard Maury Stone, Ofir Wolach, John G. Harpel, Yakov Chudnovsky, Yu Li, Rebecca G. Bagley, Angela R. Smith, James S. Blachly · 发表于：Blood · 年份：2025 · DOI：10.1182/blood.2025028357 · 被引用次数：63 · 研究领域：Acute Myeloid Leukemia Research、Multiple Myeloma Research and Treatments、Protein Degradation and Inhibitors

ABSTRACT: 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 end points were rate of complete remission (CR) or CR with partial hematologic recovery (CRh; CR + CRh), safety, and tolerability. Secondary end points included overall response rate (ORR) and duration of response. As of 18 September 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 previous lines of therapy, 35.9%; previous 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. Of 30 responders, 5 (16.7%) proceeded to hematopoietic stem cell transplant (HSCT) and 3 resumed revumenib after HSCT. Treatment-related adverse events led to treatment discontinuation in 4 patients (4.8%). Revumenib demonstrated clinically meaningful responses in ...