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Research Article: A real-world data study on long-course venetoclax combined with hypomethylating agents in unfit patients

Date Published: 2026-04-21

Abstract:
This study aimed to investigate the efficacy, safety and prognostic value of measurable residual disease (MRD) in unfit AML patients treated with long-course venetoclax combined with hypomethylating agents, so as to provide evidence for optimizing clinical low-intensity treatment regimens.A single-center retrospective analysis was conducted on unfit AML patients receiving this regimen. Clinical data were collected to explore the correlation between dynamic MRD changes at different treatment stages and patient prognosis.The long-course regimen exhibited stable clinical efficacy and effectively achieved disease remission. MRD negativity was closely associated with better prognosis, while patients with MDS-transformed AML and relapsed/refractory AML had higher recurrence risk. Adverse reactions were mainly hematological and infectious non-hematological toxicity, with controllable overall safety.Dynamic MRD monitoring provides valuable prognostic information in unfit AML patients receiving venetoclax plus hypomethylating agents. Sustained MRD negativity predicted favorable outcomes, highlighting the clinical utility of MRD-guided strategies. Due to the absence of a short-course control group, causal conclusions about treatment duration cannot be drawn, and survivorship bias should be considered. Study limitations include single-center design and limited sample size; conclusions require validation by larger multicenter prospective studies.

Introduction:
Acute myeloid leukemia (AML) can occur at any age, but it is primarily a disease of older adults, with a median age at diagnosis of 68 years ( 1 ). The majority of patients still have no identifiable predisposing factors for AML. A prior history of hematological disorders, including myelodysplastic syndromes or myeloproliferative neoplasms, is also associated with a significantly increased risk of progression to AML ( 2 , 3 ). Before the advent of venetoclax, outcomes for older patients with AML or those unfit for…

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