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Published on: March 5, 2018
MRD conversion during oral azacitidine maintenance correlates with outcomes in predominantly favorable-risk AML
Noa Hurvitz1, Irina Amitai2, Ilana Levy3,4
1Leukemia Service, Department of Hematology, Hadassah Medical Center and, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Background:
Oral azacitidine improves survival in patients with AML in first complete remission who are not candidates for allogeneic transplantation. Most favorable-risk AML patients harbor molecular markers enabling sensitive measurable residual disease (MRD) monitoring. While MRD is a well-established prognostic factor in AML, the clinical significance of MRD dynamics during maintenance therapy remains incompletely defined.
Methods:
We conducted a multicenter, real-world retrospective study of 30 patients with AML, predominantly ELN favorable-risk, treated with oral azacitidine maintenance following intensive induction-consolidation. MRD was assessed longitudinally using standardized molecular and flow-based assays. Outcomes were analyzed according to MRD status at maintenance initiation and subsequent MRD conversion.
Results:
At initiation of oral azacitidine, 47% of patients were MRD-positive. MRD conversion to negativity occurred in 64% of these patients during maintenance. Relapse-free survival (RFS) was comparable between patients who were MRD-negative at baseline and those who converted to MRD negativity (24-months restricted median RFS 577 vs. 638 days), whereas patients with persistent MRD positivity experienced early relapse (24-months restricted median RFS 63 days). Despite inferior RFS, overall survival did not significantly differ between MRD-defined groups. Patients relapsing after oral azacitidine retained sensitivity to subsequent therapies, including venetoclax-azacitidine-based regimens, with high rates of molecular response.
Conclusions:
Oral azacitidine was associated with high rates of MRD conversion, conferring RFS comparable to patients who were MRD-negative at treatment initiation. Persistent MRD identified patients at high-risk for early relapse, while effective salvage therapies mitigated overall survival differences. These findings support prospective evaluation of MRD-guided maintenance strategies in favorable-risk AML but should be considered hypothesis-generating given the retrospective design and limited cohort size. The trial is on behalf of the Israel Acute Leukemia Group.
Insights
Oral azacitidine maintenance therapy led to high rates of measurable residual disease (MRD) negativity in acute myeloid leukemia (AML) patients. Achieving MRD negativity during maintenance improved relapse-free survival, while persistent MRD indicated high relapse risk.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Oral azacitidine improves survival in acute myeloid leukemia (AML) patients in first complete remission not eligible for transplant.
- Measurable residual disease (MRD) monitoring is crucial in AML, especially in favorable-risk patients with molecular markers.
- The role of MRD dynamics during maintenance therapy in AML requires further definition.
Purpose of the Study:
- To evaluate the impact of MRD dynamics during oral azacitidine maintenance therapy on outcomes in AML patients.
- To assess the rate of MRD conversion and its correlation with relapse-free survival (RFS) and overall survival (OS).
Main Methods:
- A multicenter, real-world retrospective study of 30 AML patients receiving oral azacitidine maintenance.
- Longitudinal MRD assessment using standardized molecular and flow-based assays.
- Analysis of outcomes based on MRD status at maintenance initiation and subsequent conversion.
Main Results:
- 47% of patients were MRD-positive at oral azacitidine initiation; 64% converted to MRD negativity during maintenance.
- RFS was comparable between MRD-negative at baseline and MRD-converting patients, but significantly shorter for persistent MRD-positive patients.
- Salvage therapies, including venetoclax-azacitidine, were effective in patients relapsing after oral azacitidine, mitigating OS differences.
Conclusions:
- Oral azacitidine maintenance achieves high MRD conversion rates, improving RFS in AML patients.
- Persistent MRD identifies high-risk patients for early relapse, but salvage therapies can improve survival outcomes.
- Findings support MRD-guided maintenance strategies in favorable-risk AML, warranting prospective validation.