MRD negativity associated with superior survival outcomes in AML
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Achievement of minimal residual disease negativity appeared associated with superior DFS and OS among patients with acute myeloid leukemia, according to results of a meta-analysis published in JAMA Oncology.
Researchers observed a consistent benefit of minimal residual disease (MRD) negativity across age groups and AML subtypes, and regardless of time of MRD assessment, specimen source and MRD detection methods.
These results support MRD status as a clinical trial endpoint that could allow for faster evaluation of novel AML therapies, researchers noted.
“Pretreatment characteristics, such as age, karyotype and genomic alterations, are well-established factors associated with clinical outcomes of patients with newly diagnosed AML receiving first-line therapy,” Nicholas J. Short, MD, assistant professor in the department of leukemia at The University of Texas MD Anderson Cancer Center, and colleagues wrote. “Assessment of early response to therapy by conventional morphologic analysis also provides important information about the chemosensitivity of leukemia in an individual that cannot necessarily be estimated by pretreatment factors.”
Previous studies have shown associations of MRD persistence with higher rates of relapse and shorter DFS and OS in chronic myeloid leukemia, chronic lymphocytic leukemia and acute lymphoblastic leukemia.
Short and colleagues sought to determine the association of MRD with survival outcomes by conducting a systematic review and meta-analysis of 81 publications that included data on 11,151 patients with AML. The studies — published between Jan. 1, 2000, and Oct. 1, 2018, and identified via PubMed, Embase and MEDLINE — assessed DFS or OS by MRD status.
Researchers extracted study sample size, median patient age, median follow-up time, MRD detection method, MRD assessment time points, AML subtype, specimen source and survival outcomes. They used Bayesian hierarchical modeling to perform separate meta-analyses for DFS and OS.
Results showed an average HR for achieving MRD negativity of 0.36 (95% credible interval [CrI], 0.33-0.39) for OS and 0.37 (95% CrI, 0.34-0.4) for DFS.
Those who achieved MRD negativity had higher estimated 5-year rates of DFS (64% vs. 25%) and OS (68% vs. 34%) than those with MRD positivity.
Significant associations of MRD negativity with DFS and OS occurred among all subgroups, with the exception of MRD assessed by cytogenetics or fluorescent in situ hybridization.
“Assessment of MRD in AML in cytomorphologic remission provides important prognostic information,” Short and colleagues wrote. “Given the robustness of the association of MRD with long-term outcomes across studies, use of MRD status as an eligibility criterion or an endpoint in clinical trial design could lead to more efficient assessment of the efficacy of new drugs and combination therapies in AML.”
Using MRD negativity as a surrogate endpoint in clinical trials for AML to facilitate drug development may be beneficial moving forward, Deepa Jeyakumar, MD, and Susan O’Brien, MD, clinical researchers at Chao Comprehensive Cancer Center at University of California, Irvine, wrote in an accompanying editorial.
“Given that the standard of care therapy for AML of ‘3 + 7’ has not changed in over 40 years and yet cures only a minority of adults with AML, more rapid drug development of therapies for AML is needed,” they wrote. “Surrogate endpoints may aid in getting effective therapies to patients expeditiously while still confirming the benefit of these agents with an assessment of overall survival.”
References:
- Jeyakumar D and O’Brien S. JAMA Oncol. 2020;doi:10.1001/jamaoncol.2020.4599.
- Short NJ, et al. JAMA Oncol. 2020;doi:10.1001/jamaoncol.2020.4600.
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