Measurable Residual Disease in High-Risk Acute Myeloid Leukemia
Thomas Cluzeau1, Roberto M Lemoli2,3, James McCloskey4
1Service d'hématologie, Université Cote d'Azur, CHU de Nice, 06200 Nice, France.
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.
Insights
Measurable residual disease (MRD) monitoring shows promise for high-risk acute myeloid leukemia (AML) patients. Newer therapies like CPX-351 and venetoclax show potential for achieving MRD-negative remission, improving prognosis.
Area of Science:
- Hematology
- Oncology
- Molecular Diagnostics
Background:
- High-risk acute myeloid leukemia (AML) presents challenges in achieving durable remission with conventional chemotherapy.
- Specific patient groups, including those with therapy-related AML or specific genetic mutations, face poorer prognoses.
- Emerging therapies offer new possibilities for achieving deeper remissions in high-risk AML.
Purpose of the Study:
- To evaluate the prognostic significance of measurable residual disease (MRD) assessments in acute myeloid leukemia (AML).
- To review the efficacy of newer agents, CPX-351 and venetoclax, in achieving MRD-negative remission in high-risk AML populations.
- To highlight the need for standardized MRD methodologies in clinical practice and future research.
Main Methods:
- Review of retrospective studies and clinical trials involving CPX-351 and venetoclax in adult and pediatric AML.
- Analysis of MRD-negativity rates in various high-risk AML subgroups.
- Discussion of current limitations in MRD assessment methodologies.
Main Results:
- CPX-351 demonstrated MRD-negativity rates of 36-64% in newly diagnosed high-risk adult AML and 84% in relapsed pediatric AML.
- Venetoclax, in combination therapies, showed MRD-negativity rates of 33-53% in older adults with newly diagnosed AML and 65% in relapsed/refractory pediatric AML.
- Significant variability exists in MRD assessment techniques, limiting cross-study comparisons.
Conclusions:
- Newer agents like CPX-351 and venetoclax show promise in achieving MRD-negative remission for high-risk AML patients.
- Standardization of MRD detection methods is crucial for reliable prognostic assessment and treatment guidance.
- Routine MRD monitoring is recommended for comprehensive AML management.
More Related Videos
09:01Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up
Published on: March 26, 2018
07:38Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025