Clinical Outcomes in Acute Myeloid Leukemia Patients with High MECOM Expression Treated with Venetoclax-Based Regimens: A Single-Institution Retrospective Analysis

Background: High MECOM expression (MECOM+) in acute myeloid leukemia (AML) represents a rare, aggressive subtype with poor prognosis. This study assesses clinical outcomes in MECOM+ AML patients received with venetoclax-based therapies. Methods: Among 230 non-M3 AML cases between August 2018 and December 2024, 14 (6.1%) harbored MECOM overexpression. After excluding two untreated patients, 11 received venetoclax-based regimens (n=6) or standard 7+3 chemotherapy (n=5), and one received supportive care. Outcomes, including complete remission (CR), CR with incomplete hematologic recovery (CRi), overall survival (OS), and event-free survival (EFS) were retrospectively analyzed. Results: The cohort exhibited a median CR rate of 50%, OS of 6 months, and EFS of 1 month. Estimated 1-year OS and EFS rates were 46.3% and 41.7%, respectively. Venetoclax-based regimens showed comparable 1-year OS (40% vs 50%, P=0.94) and EFS (33.3% vs 50%, P=0.58) to non-venetoclax therapies. Venetoclax plus intensive chemotherapy significantly improved CR/CRi rates (2/2, 3/5 vs. 1/4) and prolonged OS (20.5 months, 6 months vs. 6 months) compared to standard chemotherapy or venetoclax-azacytidine. CR patients achieved superior 1-year OS and EFS rates of 83.3%. Concurrent cytogenetic abnormalities (-17/abn(17p), -7/del(7q), and monosomal karyotype) were associated with reduced CR rates (1/2, 4/8, and 2/5) and shorter median OS(3, 5.5, and 5 months, respectively). Conclusions: MECOM+ AML has a dismal prognosis. Venetoclax with intensive chemotherapy and transplant improved CR/CRi and OS in fit patients, while elderly and unfit patients on venetoclax-azacytidine fared poorly. Large-scale prospective studies are needed to optimize treatment for this high-risk AML subgroup.