The prognosis of newly diagnosed patients with
acute myeloid leukemia is still unfavorable in the majority of cases within the intermediate and mainly adverse genetic risk group but also in a considerable fraction of favorable-risk patients, mainly due to recurrence of disease after complete remission achievement or, less frequently, primary refractoriness. Besides genetic classification at diagnosis, post-treatment prognostic factors include measurable residual disease evaluation in patients
in complete remission and in most cases measurable residual disease (MRD) positivity predicts hematologic relapse potentially allowing early therapeutic intervention. Currently, the most commonly used methods for detection of
minimal residual disease are multiparameter flow cytometry and quantitative PCR, applicable to around 90% and 50% of patients, respectively. In addition, in > 90% of
acute myeloid leukemia (AML) patients, molecular aberrations can be identified by next-generation sequencing, a technology that is widely used in clinical practice for the initial mutational screening at the time of diagnosis but more often, for MRD detection because its flexibility allows almost every mutated gene to be used as an MRD marker. Threshold levels of residual disease and correlation with outcome have been thoroughly studied and established in younger patients treated with intensive induction and
consolidation chemotherapy as well as after
allogeneic transplantation. Yet, experience on MRD monitoring and interpretation in patients treated with low-intensity regimens, including new agents, is still limited. The updated armamentarium of anti-leukemic agents includes the BCL-2 inhibitor
venetoclax, which demonstrated good tolerability, high response rates, and prolonged overall survival when combined with hypomethylating agents or low dose
cytarabine in patients considered elderly/"unfit" to tolerate intensive regimens. Although remissions with negative
minimal residual disease clearly translated into improved outcomes after intensive treatments, data supporting the same evidence in patients receiving low-intensity
venetoclax-based treatments are not still consolidated. We here review and discuss more recent data on the
minimal residual disease interpretation and role in AML patients treated with
venetoclax-based combinations.