Undetectable Measurable Residual Disease is Associated with Improved Outcomes in AML Irrespective of Treatment Intensity.

Acute myeloid leukemia (AML) can be treated with either high or low-intensity regimens. Highly sensitive assays for measurable residual disease (MRD) now allow for a more precise assessment of response quality. We hypothesized that treatment intensity may not be a key predictor of outcomes assuming an optimal response to therapy is achieved. We performed a single-center retrospective study including 635 patients with newly diagnosed AML responding to either intensive cytarabine/anthracycline-based chemotherapy (IA, n=385) or low-intensity venetoclax-based regimens (LOW + VEN, n=250) and who had adequate flow cytometry-based MRD testing performed at the time of best response. The median overall survival (OS) was 50.2, 18.2, 13.6, and 8.1 months for the IA MRD(-), LOW + VEN MRD(-), IA MRD(+), and LOW + VEN MRD(+) cohorts, respectively. The 2-year cumulative incidence of relapse (CIR) was 41.1%, 33.5%, 64.2%, and 59.9% for the IA MRD(-), LOW + VEN MRD(-), IA MRD(+), and LOW + VEN MRD(+) cohorts, respectively. The CIR was similar between patients within MRD categories irrespective of the treatment regimen received. The IA cohort was enriched for younger patients and more favorable AML cytogenetic/molecular categories. By multivariate analysis (MVA), age, best response (CR/CRi/MLFS), MRD status, and ELN 2017 risk remained significantly associated with OS, whereas best response, MRD status, and ELN 2017 risk were significantly associated with CIR. Treatment intensity was not significantly associated with either OS or CIR. Achievement of MRD-negative complete remission should be the key objective of AML therapy in both high- and low-intensity treatment regimens.