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Original Investigation
October 8, 2020

Association of Measurable Residual Disease With Survival Outcomes in Patients With Acute Myeloid Leukemia: A Systematic Review and Meta-analysis

Author Affiliations
  • 1Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston
  • 2Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pennsylvania
  • 3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston
  • 4Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
  • 5Institute of Infection and Immunity, University of Birmingham, Birmingham, United Kingdom
  • 6Laboratory of Myeloid Malignancies, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
JAMA Oncol. Published online October 8, 2020. doi:10.1001/jamaoncol.2020.4600
Key Points

Question  What is the association between measurable residual disease (MRD) and survival outcomes in patients with acute myeloid leukemia?

Findings  In a systematic review and meta-analysis of 81 publications reporting on 11 151 patients with acute myeloid leukemia, the estimated 5-year disease-free survival was 64% for patients without MRD and 25% for those with MRD. The estimated overall survival was 68% for patients without MRD and 34% for those with MRD.

Meaning  The findings of this study suggest that, in patients with acute myeloid leukemia, achievement of MRD negativity is associated with superior long-term survival and warrants consideration as a clinical trial end point that may allow for more rapid evaluation of the efficacy of novel therapies.

Abstract

Importance  Measurable residual disease (MRD) refers to neoplastic cells that cannot be detected by standard cytomorphologic analysis. In patients with acute myeloid leukemia (AML), determining the association of MRD with survival may improve prognostication and inform selection of efficient clinical trial end points.

Objective  To examine the association between MRD status and disease-free survival (DFS) and overall survival (OS) in patients with AML using scientific literature.

Data Sources  Clinical studies on AML published between January 1, 2000, and October 1, 2018, were identified via searches of PubMed, Embase, and MEDLINE.

Study Selection  Literature search and study screening were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies that assessed DFS or OS by MRD status in patients with AML were included. Reviews, non–English-language articles, and studies reporting only outcomes after hematopoietic cell transplantation or those with insufficient description of MRD information were excluded.

Data Extraction and Synthesis  Study sample size, median patient age, median follow-up time, MRD detection method, MRD assessment time points, AML subtype, specimen source, and survival outcomes were extracted. Meta-analyses were performed separately for DFS and OS using bayesian hierarchical modeling.

Main Outcomes and Measures  Meta-analyses of survival probabilities and hazard ratios (HRs) were conducted for OS and DFS according to MRD status.

Results  Eighty-one publications reporting on 11 151 patients were included. The average HR for achieving MRD negativity was 0.36 (95% bayesian credible interval [CrI], 0.33-0.39) for OS and 0.37 (95% CrI, 0.34-0.40) for DFS. The estimated 5-year DFS was 64% for patients without MRD and 25% for those with MRD, and the estimated OS was 68% for patients without MRD and 34% for those with MRD. The association of MRD negativity with DFS and OS was significant for all subgroups, with the exception of MRD assessed by cytogenetics or fluorescent in situ hybridization.

Conclusions and Relevance  The findings of this meta-analysis suggest that achievement of MRD negativity is associated with superior DFS and OS in patients with AML. The value of MRD negativity appears to be consistent across age groups, AML subtypes, time of MRD assessment, specimen source, and MRD detection methods. These results support MRD status as an end point that may allow for accelerated evaluation of novel therapies in AML.

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