In a systematic review and meta-analysis reported in JAMA Oncology, Nicholas J. Short, MD, and colleagues found that minimal (or measurable) residual disease (MRD) negativity is associated with superior disease-free and overall survival in patients with acute myeloid leukemia (AML).
As stated by the investigators, “In patients with AML, determining the association of MRD with survival may improve prognostication and inform selection of efficient clinical trial endpoints.”
“The findings of this meta-analysis suggest that achievement of MRD negativity is associated with superior disease-free survival and overall survival 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 endpoint that may allow for accelerated evaluation of novel therapies in AML.”— Nicholas J. Short, MD, and colleagues
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Study Details
The meta-analysis included 81 articles (published between January 2000 and October 2018) that assessed disease-free or overall survival by MRD status in a total of 11,151 patients. Of these, 17 articles (n = 3,118) reported on overall survival alone, 20 (n =1,783) on disease-free survival alone, and 44 (6,250) on both. Meta-analyses for disease-free survival and overall survival were performed separately using Bayesian hierarchical modeling.
Key Findings
The average hazard ratio for achieving MRD negativity was 0.37 (95% credible interval = 0.340.40) for disease-free survival and 0.36 (95% credible interval = 0.33–0.39) for overall survival.
Estimated 5-year disease-free survival was 64% for patients without MRD vs 25% for those with MRD. The average hazard ratio was 0.37 (95% credible interval = 0.34–0.40).
Estimated 5-year overall survival was 68% for patients without MRD vs 34% for those with MRD. The average hazard ratio was 0.36 (95% credible interval = 0.33–0.39).
The difference in 5-year restricted mean survival time between the MRD-negative group and the MRD-positive group was 19.61 months (95% credible interval = 17.33–21.92 months) for disease-free survival and 15.37 months (95% credible interval = 13.58–17.19 months) for overall survival.
MRD negativity was associated with superior disease-free and overall survival, regardless of age group (adult or pediatric), MRD assessment time point (induction, during consolidation, or after consolidation), AML subgroup (core-biding factor or non–core binding factor), or specimen source (bone marrow or peripheral blood). Among MRD detection methods, the benefit of MRD negativity with MRD detected by cytogenetics/fluorescence in situ hybridization was not significant for disease-free survival (average hazard ratio = 0.65, 95% credible interval = 0.34–1.23) or overall survival (average hazard ratio = 0.77, 95% credible interval = 0.39–1.56).
The investigators concluded, “The findings of this meta-analysis suggest that achievement of MRD negativity is associated with superior disease-free survival and overall survival 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 endpoint that may allow for accelerated evaluation of novel therapies in AML.”
Farhad Ravandi, MD, of the Department of Leukemia, The University of Texas MD Anderson Cancer Center, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute and National Institutes of Health. For full disclosures of the study authors, visit jamanetwork.com.
