MECOM fusion partner and bone marrow blast percentage influence outcomes of patients with MECOM rearranged acute myeloid leukaemia

Summary MECOM rearrangements ( MECOM ‐r) are acute myeloid leukaemia (AML)‐defining, regardless of blast percentage or MECOM fusion partner. We sought to investigate if blast percentage or MECOM ‐r partner was associated with overall survival (OS). We included 152 adult patients with newly diagnosed MECOM ‐r and classified blast percentage into <20% or ≥20% and MECOM ‐r partner into classic ( GATA2::MECOM ) or variant (others). Thirty‐one per cent had <20% blasts, with 69% having ≥20%; 57% had classic and 43% variant MECOM ‐r. Treatment was with intensive chemotherapy (IC) in 41% and low‐intensity therapy (LIT) in 59%. Composite complete remission rates were similar between IC (50%) and LIT (48%, p = 0.99). The median OS was 17 months (95% confidence interval CI, 12–not estimable NE) for <20% blasts, compared with 9 months (95% CI, 6–10) for ≥20% blasts ( p < 0.01). On multivariate analysis, ≥20% blasts were associated with worse OS (hazard ratio HR 1.9, 95% CI, 1.2–3.2, p < 0.01), independent of age, MECOM ‐r partner, additional cytogenetic abnormalities, treatment intensity, addition of venetoclax and stem cell transplant (SCT). HR for IC was 2.0 (95% CI, 1.1–3.7, p = 0.03). In <20% blasts, variant MECOM ‐r was independently associated with a reduced hazard of death (HR 0.2 95% CI, 0.1–0.8, p < 0.01). MECOM ‐r AML is a heterogenous entity; consideration should be given to LIT approaches.