Revumenib for patients with relapsed or refractory (R/R) KMT2Ar acute leukemia: Outcomes by leukemia type in the phase 2 AUGMENT-101 study

作者：Ibrahim Aldoss, Ghayas C. Issa, James S. Blachly, Michael J. Thirman, Gabriel N. Mannis, Martha Arellano, John F. DiPersio, Elie Traer, C. Michel Zwaan, Neerav Shukla, Branko Cuglievan, Carolyn Grove, Matthew Greenwood, Christine M. McMahon, Alexander E. Perl, Richard M. Stone, Cristina Papayannidis, David S. Dickens, Maël Heiblig, Andrius Žučenka, Pau Montesinos, Ioannis Mantzaris, Tibor Kovacsovics, Paul J. Shami, Li Yu, Rebecca G. Bagley, Angela R. Smith, Eytan M. Stein · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-1001 · 被引用次数：5 · 研究领域：Acute Myeloid Leukemia Research、Protein Degradation and Inhibitors、Histone Deacetylase Inhibitors Research

Abstract BACKGROUND Patients (pts) with lysine methyltransferase 2A–rearranged (KMT2Ar)acute leukemia (AL) have a poor prognosis. The menin-KMT2A interaction is a key driver of leukemogenesis. Revumenib is a first-in-class, oral, selective inhibitor of the menin-KMT2A interaction. The AUGMENT-101 phase 2 analysis included pts with different leukemia types: ALL, AML, and mixed-phenotype AL (MPAL). Recent results (data cutoff [DCO]: Feb 29, 2024; efficacy-evaluable population, n=97; safety population, N=116) showed a complete remission (CR) or CR with partial hematologic recovery (CR+CRh) rate of 23% and an overall response rate (ORR) of 64% as well as a generally well-tolerated safety profile (Aldoss et al. ASH 2024. Abstract 211). Here we report outcomes by AL subtype (ALL, AML, and MPAL) in pts with KMT2Ar AL from the DCO (Feb 29, 2024).METHODS Pts aged ≥30 d with R/R KMT2Ar AL were eligible to enroll and receive revumenib 163 mg (95 mg/m2 if body weight <40 kg) every 12 h with a strong CYP3A4 inhibitor in 28-d continuous cycles. Treatment continued until unacceptable toxicity, disease progression, or lack of response after ≤4 cycles. Primary endpoints were CR+CRh rate, safety, and tolerability. Key secondary endpoints included ORR (composite CR+MLFS+partial remission) and duration of response (DOR). Pts with centrally confirmed KMT2Ar AL and ≥5% baseline bone marrow blasts within 28 d prior to the start of study treatment made up the efficacy-evaluable population. Measurabl...