Ziftomenib in Relapsed or Refractory NPM1 -Mutated AML

作者：Eunice S. Wang, Pau Montesinos, James M. Foran, Harry P. Erba, Eduardo Rodríguez‐Arbolí, Kateryna Fedorov, Maël Heiblig, Florian H. Heidel, Jessica K. Altman, Maria R. Baer, Lionel Adès, Kristen Pettit, Pierre Péterlin, Cristina Papayannidis, Céline Berthon, Roland B. Walter, Mithun Vinod Shah, Suresh Kumar Balasubramanian, Mohamad Khawandanah, Olga Salamero Garcia, Julie Bergeron, Yazan F. Madanat, Gail J. Roboz, Matthew Ulrickson, Robert L. Redner, James McCloskey, Arnaud Pigneux, Adolfo de la Fuente, Amitava Mitra, Harris S. Soifer, Marilyn Tabachri, Zijing Zhang, Marcie Riches, Daniel Corum, Mollie Leoni, Ghayas C. Issa, Amir T. Fathi, Lionel Adès, Jessica K. Altman, Maria R. Baer, Suresh Kumar Balasubramanian, Frédéric Barabé, Julie Bergeron, Teresa Bernal del Castillo, Céline Berthon, Adolfo de la Fuente, Dries Deeren, Mahmoud Elsawy, Harry P. Erba, Jordi Esteve Reyner, Amir T. Fathi, Kateryna Fedorov, James M. Foran, Caterina Giannini, Maël Heiblig, Florian H. Heidel, Ghayas C. Issa, Mohamad Khawandanah, Francesco Lanza, Yazan F. Madanat, James McCloskey, Pau Montesinos, Cristina Papayannidis, Agustín Penedo, Pierre Péterlin, Kristen Pettit, Arnaud Pigneux, Robert L. Redner, Gail J. Roboz, Eduardo Rodríguez‐Arbolí, Olga Salamero Garcia, Adrian Schwarzer, Mithun Vinod Shah, Matthew Ulrickson, Adriano Venditti, Roland B. Walter, Eunice S. Wang · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco-25-01694 · 被引用次数：33 · 研究领域：Acute Myeloid Leukemia Research、Myeloproliferative Neoplasms: Diagnosis and Treatment、Multiple Myeloma Research and Treatments

PURPOSE Ziftomenib—a potent, highly selective, oral menin inhibitor—was well tolerated and demonstrated encouraging clinical activity as monotherapy for relapsed/refractory NPM1 -mutated ( NPM1 -m) and KMT2A -rearranged AML in the KOMET-001 phase I trial. METHODS In the registration-enabling phase II part of KOMET-001, patients with relapsed/refractory NPM1 -m AML received ziftomenib 600 mg once daily. The primary end point was the rate of complete remission with full hematologic recovery (CR)/CR with partial hematologic recovery (CRh). RESULTS From January 26, 2023, to May 13, 2024, 92 patients (median age, 69 years [range, 33-84]) were treated. The primary end point was met, with a CR/CRh rate of 22% (95% CI, 14 to 32; P = .0058); 61% were negative for measurable residual disease. Overall response rate was 33% (95% CI, 23 to 43), with a median duration of 4.6 months (95% CI, 2.8 to 7.4). Prespecified subgroup analyses showed comparable CR/CRh regardless of previous therapy, including venetoclax, or type of comutations. Median overall survival was 6.6 months (95% CI, 3.6 to 8.6). Common grade ≥3 treatment-emergent adverse events were febrile neutropenia (26%), anemia (20%), and thrombocytopenia (20%). Differentiation syndrome occurred in 25% of patients (15% grade 3; no grade 4-5) and was manageable with protocol-defined mitigation. Three patients (3%) discontinued treatment because of ziftomenib-related adverse events. CONCLUSION Ziftomenib demonstrated significant clinical...