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

Acute myeloid leukemia (AML) harboring KMT2A rearrangement (KMT2Ar) was generally associated with poor prognosis. We enrolled 490 patients with KMT2Ar 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 KMT2Ar AML in China.