Ultra-high-sensitivity next-generation sequencing–based MRD predicts outcome in intensively treated older patients with acute myeloid leukemia: results from the ALFA-1200 cohort - Report - MDSpire
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Ultra-high-sensitivity next-generation sequencing–based MRD predicts outcome in intensively treated older patients with acute myeloid leukemia: results from the ALFA-1200 cohort
Clinical Report: Next-Generation Sequencing with Ultra-High Sensitivity for MRD Assessment Predicts Outcomes in Older Patients with Acute Myeloid Leukemia: Findings from the ALFA-1200 Study
Overview
This study evaluates the prognostic value of ultra-high-sensitivity next-generation sequencing (UHS-NGS) for measurable residual disease (MRD) in older patients with acute myeloid leukemia (AML). Findings indicate that MRD positivity significantly correlates with higher relapse rates and lower overall survival in this population.
Background
Measurable residual disease (MRD) is a critical biomarker for risk stratification in acute myeloid leukemia (AML), particularly in assessing treatment response and long-term outcomes. While MRD assessment has been extensively studied in younger patients, older patients are often underrepresented in research, despite their unique disease characteristics and treatment challenges. This study aims to fill the gap by investigating the clinical relevance of UHS-NGS MRD in older AML patients treated with intensive chemotherapy.
Data Highlights
Parameter
Value
Median VAF
0.054% (range: [0.0046–51.5%])
MRD positivity at sensitivity threshold of 10⁻⁴
49 of 93 patients (52.7%)
2-year cumulative incidence of relapse (MRD positive vs negative)
73% vs 38% (p = 0.003)
2-year relapse-free survival (RFS) (MRD positive vs negative)
23% vs 55% (p = 0.008)
2-year overall survival (OS) (MRD positive vs negative)
54% vs 79% (p = 0.041)
Key Findings
UHS-NGS MRD assessment was performed on 93 older AML patients post-IDAC.
MRD positivity was significantly higher in adverse-risk groups (70%) compared to favorable (53%) and intermediate (36%) risk groups (p = 0.03).
Patients with MRD positivity had a significantly higher 2-year cumulative incidence of relapse (73% vs 38%, p = 0.003).
MRD positivity was associated with inferior relapse-free survival (RFS 23% vs 55%, p = 0.008) and overall survival (OS 54% vs 79%, p = 0.041).
Persistence of multiple myelodysplasia-related gene mutations correlated with worse outcomes in patients with detectable MRD.
Clinical Implications
The findings suggest that UHS-NGS MRD assessment can provide valuable prognostic information for older AML patients, aiding in the identification of those at higher risk for relapse. Clinicians may consider incorporating UHS-NGS MRD results into treatment decision-making processes for this population.
Conclusion
UHS-NGS MRD assessment retains significant prognostic value in older AML patients, highlighting the need for tailored approaches in this demographic. Further research is warranted to optimize MRD interpretation and management strategies.
