Measureable residual disease (MRD)-negativity is linked with improved survival among patients with acute myeloid leukemia (AML), and may qualify as an effective clinical trial endpoint in this disease setting, according to a study published in JAMA Oncology.

MRD persistence is linked with disease-free survival (DFS) and overall survival (OS) in a number of leukemia settings, including chronic myeloid leukemia, chronic lymphocytic leukemia, and acute lymphoblastic leukemia. Many studies also support links between DFS and OS in AML across patient subgroups, despite the high clinical heterogeneity in this patient population.

There is a high degree of discrepancy in methodology among studies showing a link between MRD and survival in AML. Different MRD detection methods, such as multiparameter flow cytometry and polymerase chain reaction, as well as different specimen sources, are frequently used. For this reason, there is no standard for MRD detection for the guidance of clinical decision-making across the AML spectrum. To address this issue, the authors of the present study conducted a meta-analysis of research into the connection between MRD status and survival in AML.

Overall, researchers identified and evaluated 81 studies representing data from 11,151 patients with AML. All studies were published from January 2000 to October 2018.


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Compared with patients who were MRD-positive, MRD-negative patients had better OS and DFS outcomes. The hazard ratio across subgroups for reaching MRD negativity was 0.36 for OS and 0.37 for DFS, with persistent significance across patient subgroups. Among patients reaching MRD negativity, the 5-year DFS and OS rates were 64% and 68%, respectively. Among patients not reaching MRD negativity, the 5-year DFS and OS rates were 25% and 34%, respectively.

MRD negativity assessed by cytogenetics or fluorescent in situ hybridization did not predict for DFS or OS.

“In this large-cohort meta-analysis, achievement of MRD negativity was associated with superior DFS and OS in patients with AML, an association that was observed across ages, disease subtypes, time of assessment, specimen source, and most MRD detection methods,” the authors wrote.

Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

Reference

Short NJ, Zhou S, Fu C, et al. Association of measurable residual disease with survival outcomes in patients with acute myeloid leukemia: a systematic review and meta-analysis. JAMA Oncol. Published online October 8, 2020. doi:10.1001/jamaoncol.2020.4600