Bleximenib in combination with intensive chemotherapy: A phase 1b study in newly diagnosed Acute Myeloid Leukemia with KMT2A or NPM1 alterations

作者：H. Döhner, Andre C. Schuh, Christian Récher, J. O'Nions, Ibrahim Aldoss, A. Alfonso-Piérola, Alicia Allred, J. Alonso‐Dominguez, Laura Barreyro, P. Bories, Nikki Daskalakis, M. D. Della Porta, Amber D’Souza, James Dugan, Jordi Esteve, Amir T Fathi, Lucille Ferrante, Stan Gaj, S. Garciaz, A. Garrido, O. Salamero, Christina Drenberg Guttke, E. Gyan, Brett Hiebert, E. Jabbour, M. Jentzsch, H. Kantarjian, Marina Konopleva, J. Krönke, M. Hütter-Krönke, C. Loefgren, Oliver Lomas, Valentina Mancini, Ioannis Mantzaris, Daniel Morillo, Kathryn Packman, C. Papayannidis, U. Philippar, U. Platzbecker, Sara Garrido Paniagua, Naa Sackey, T. Sauer, Dr. Emma Searle, Prathap Nagaraja Shastri, D. Trancucci, N. Tovar, Nicolas Vallet, Lachlin Vaughan, Paresh Vyas, Andrew Wei, C. Röllig · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-5199 · 被引用次数：12

Objective Bleximenib is a potent, selective menin inhibitor with activity in NPM1-mutated (NPM1m)or KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML), now in Phase 3 development in combination with AML-directed therapies. Previous data have shown an acceptable safety and efficacy profile in participants (pts) with newly diagnosed (ND) NPM1m or KMT2Ar AML treated with bleximenib in combination with intensive chemotherapy (IC) (Recher C, ASH 2024). We now report updated safety and efficacy data (clinical cut-off: July 2025) from this combination treatment in IC-eligible ND AML pts (Cohort C1). Methods In the ALE1002 Phase 1b, multicenter, dose-finding study (NCT05453903), pts in Cohort C1 received a standard '7+3' regimen of cytarabine 200 mg/m2/day and daunorubicin 60 mg/m2/day intravenous (IV) or idarubicin 12 mg/m2/day IV in combination with bleximenib. Bleximenib was administered by mouth at 30–100 mg twice daily (BID) continuously starting on Day 4 of induction, including during count recovery. Pts who achieved a complete remission (CR) received consolidation therapy with up to 4 cycles of intermediate-dose cytarabine plus bleximenib. Those not proceeding to allogeneic hematopoietic stem cell transplant could receive bleximenib in continuation for up to 12 months. The safety dataset includes all dosed pts receiving bleximenib 30–100 mg BID in combination with '7+3'. Relative dose intensity (RDI) is the total bleximenib dose received divided by total planned doses of ...