Measurable Residual Disease in High-Risk Acute Myeloid Leukemia

SIMPLE SUMMARY: Assessment of measurable residual disease (MRD) identifies small numbers of acute myeloid leukemia (AML) cells that may remain after initiating treatment. The achievement of MRD negativity (no detectable AML cells remaining) typically predicts better outcomes for patients with AML. Some patients with AML have disease characteristics that put them at a higher risk of treatment failure or relapse; while outcomes for patients with high-risk AML are historically poor with traditional chemotherapy regimens, newer chemotherapy formulations (i.e., CPX-351) and targeted therapies may be more effective in achieving MRD negativity in these patients. Currently, there is no agreement on the best method for determining whether a patient has achieved MRD negativity, and the use of several different methods makes it difficult to compare outcomes across studies. Despite these challenges, regular monitoring of patients for the achievement of MRD negativity will become increasingly important in the routine management of patients with high-risk AML. ABSTRACT: Mounting evidence suggests measurable residual disease (MRD) assessments are prognostic in acute myeloid leukemia (AML). High-risk AML encompasses a subset of AML with poor response to therapy and prognosis, with features such as therapy-related AML, an antecedent hematologic disorder, extramedullary disease (in adults), and selected mutations and cytogenetic abnormalities. Historically, few patients with high-risk AML achieved deep and durable remission with conventional chemotherapy; however, newer agents might be more effective in achieving MRD-negative remission. CPX-351 (dual-drug liposomal encapsulation of daunorubicin/cytarabine at a synergistic ratio) demonstrated MRD-negativity rates of 36–64% across retrospective studies in adults with newly diagnosed high-risk AML and 84% in pediatric patients with first-relapse AML. Venetoclax (BCL2 inhibitor) demonstrated MRD-negativity rates of 33–53% in combination with hypomethylating agents for high-risk subgroups in studies of older adults with newly diagnosed AML who were ineligible for intensive therapy and 65% in combination with chemotherapy in pediatric patients with relapsed/refractory AML. However, there is no consensus on optimal MRD methodology in AML, and the use of different techniques, sample sources, sensitivity thresholds, and the timing of assessments limit comparisons across studies. Robust MRD analyses are needed in future clinical studies, and MRD monitoring should become a routine aspect of AML management.