Treatment of acute myeloid leukemia with inv(3) or t(3;3): A single-center retrospective cohort study and literature review.

INTRODUCTION: AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2) is a rare, adverse-risk subtype with poor outcomes and limited regimen-specific data. The optimal partner for hypomethylating agent (HMA)-based therapy remains uncertain. PATIENTS AND METHODS: Adults with AML harboring inv(3)/t(3;3) who received HMA plus lenalidomide or HMA plus venetoclax at a single center between January 2012 and April 2026 were included. Patients were grouped by index regimen. Responses were assessed using the 2022 European LeukemiaNet criteria. Outcomes included best overall response, cycle 1 response, overall survival, response duration, hematologic recovery, transplant-related outcomes, and safety. RESULTS: Eighteen patients were included, with 9 in each cohort. Best overall response occurred in 4 patients (44.4%) receiving HMA plus lenalidomide and 3 patients (33.3%) receiving HMA plus venetoclax (P = 1.000). Median overall survival was 20.3 versus 5.5 months, respectively (log-rank P = .033). Median response duration was 7.0 versus 8.5 months, respectively. Prolonged thrombocytopenia and neutropenia were common in both cohorts. CONCLUSION: HMA plus venetoclax did not demonstrate a clear response advantage over HMA plus lenalidomide. Novel strategies are needed to improve response durability and long-term outcomes in MECOM-rearranged AML.