Characteristics and Prognostic Implications in Newly Diagnosed KMT2Ar AML : A Multicenter Study of the ECLA Group

ABSTRACT Acute myeloid leukemia (AML) harboring KMT2A rearrangement ( KMT2A r) was generally associated with poor prognosis. We enrolled 490 patients with KMT2A r from the East China Leukemia Alliance between March 2013 and August 2025. KMT2A::MLLT3 was the most frequent KMT2Ar (31.6%), followed by KMT2A::MLLT4 (25.1%), KMT2A::ELL (20%), and KMT2A::MLLT10 (12.7%). KMT2A::MLLT4 showed an inferior prognosis. The most co‐occurring gene mutations were KRAS (20.1%), NRAS (19.0%), TET2 (10.2%), WT1 (8.6%), and PTPN11 (7.4%). Trisomy 8 was more common in patients < 60 years, while FLT3‐ITD was only detected in patients < 60 years. With a median follow‐up time of 42.6 months, the median overall survival (OS) of all patients was 30.9 months, and the 3‐year OS rate was 49.9%. Patients treated with venetoclax plus intensive chemotherapy (Ven+IC) showed the best composite complete remission (CRc) rate and OS compared to intensive chemotherapy, venetoclax plus reduced‐intensive chemotherapy, and reduced‐intensive chemotherapy (CRc rate: 89.5% vs. 62.4% vs. 57.3% vs. 61.4%; median OS: not reached vs. 39.9 months vs. 34.8 months vs. 12.7 months). Multivariate analysis identified multiparameter flow cytometry minimal residual disease negativity post‐induction therapy, allogeneic hematopoietic stem cell transplantation, and Ven+IC as independent favorable prognostic factors for event‐free survival (EFS), and KMT2A::MLLT4 fusion, EVI1 overexpression were independent unfavorable prognostic factors for EFS. In summary, our study showed characteristics and prognostic implications in newly diagnosed KMT2A r AML in China.