Real-World Experience of Measurable Residual Disease Response and Prognosis in Acute Myeloid Leukemia Treated with Venetoclax and Azacitidine

SIMPLE SUMMARY: More than 90% of patients with acute myeloid leukemia carry aberrant markers that can be detected using flow cytometry. Monitoring low levels of residual disease after treatment (measurable residual disease) is an important biomarker to assess the efficacy of treatment and can identify patients who may eventually relapse. Our retrospective study aimed to determine the potential value of MRD for prognosticating outcomes in AML patients treated with less intensive chemotherapy. In 63 patients with newly diagnosed AML, we found that detectable residual disease by flow cytometry was associated with a higher incidence of relapse, and shorter progression-free and overall survival. We also confirmed that the threshold of measurable disease affecting outcomes is 0.1%. MRD is useful in patients to monitor AML patients treated with less intensive therapy. ABSTRACT: The prognostic value of measurable residual disease (MRD) by flow cytometry in acute myeloid leukemia (AML) patients treated with non-intensive therapy is relatively unexplored. The clinical value of MRD threshold below 0.1% is also unknown after non-intensive therapy. In this study, MRD to a sensitivity of 0.01% was analyzed in sixty-three patients in remission after azacitidine/venetoclax treatment. Multivariable cox regression analysis identified prognostic factors associated with cumulative incidence of relapse (CIR), progression-free survival (PFS) and overall survival (OS). Patients who achieved MRD < 0.1% had a lower relapse rate than those who were MRD ≥ 0.1% at 18 months (13% versus 57%, p = 0.006). Patients who achieved an MRD-negative CR had longer median PFS and OS (not reached and 26.5 months) than those who were MRD-positive (12.6 and 10.3 months, respectively). MRD < 0.1% was an independent predictor for CIR, PFS, and OS, after adjusting for European Leukemia Net (ELN) risk, complex karyotype, and transplant (HR 5.92, 95% CI 1.34–26.09, p = 0.019 for PFS; HR 2.60, 95% CI 1.02–6.63, p = 0.046 for OS). Only an MRD threshold of 0.1%, and not 0.01%, was predictive for OS. Our results validate the recommended ELN MRD cut-off of 0.1% to discriminate between patients with improved CIR, PFS, and OS after azacitidine/venetoclax therapy.