Leukemia · 2025
Characteristics and outcomes of newly diagnosed acute myeloid Leukemia with KMT2A rearrangements.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Bataller Alex, Goulart Hannah E, Issa Ghayas C, DiNardo Courtney D, Daver Naval, Kadia Tapan, Bazinet Alexandre, Bouligny Ian M, Senapati Jayastu, Haddad Fadi G, Borthakur Gautam, Sasaki Koji, Short Nicholas J, Yilmaz Musa, Montalban-Bravo Guillermo, Tang Guiling, Loghavi Sanam, Garcia-Manero Guillermo, Ravandi Farhad, Kantarjian Hagop, Jabbour Elias
Аннотация
Acute myeloid leukemia (AML) with KMT2A rearrangement (KMT2Ar) has poor outcomes. We analyzed 1,611 patients with AML and 4.3% demonstrated rearrangements in KMT2A. Signaling-related genes (NRAS 30%, KRAS 23% and FLT3-TKD 16%) were the most frequently mutated in patients with KMT2Ar AML. Patients treated with intensive chemotherapy (IT) achieved a complete remission (CR)/CR with incomplete blood count recovery (CRi) rate of 81%, and when combined with venetoclax, the CR/CRi rate increased to 100%. Patients treated with low intensity treatment (LIT) achieved an CR/CRi rate of 33%, and when combined with venetoclax, the CR/CRi rate was 61%. For patients treated with IT, the 5-year overall survival (OS) and event-free survival (EFS) rates were 66% and 64%, respectively, compared with 7% in those treated with LIT. Thirty-nine patients (57%) underwent allogeneic stem cell transplantation after achieving CR/CRi. For patients treated with LIT, multivariate analysis demonstrated that N/KRAS mutations were predictive for OS (HR 2.93, 95% CI 1.18-7.29, P = 0.021) and EFS (HR 3.51, 95% CI 1.35-9.24, P = 0.01). In summary, outcomes in KMT2Ar AML have improved over years in patients treated with IT, whereas those treated with LIT continue to show poor survival, highlighting the need for novel combinations.