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In Acute Myeloid Leukemia, Measurable Residual Disease Correlates With Survival

Acute myeloid leukemia.

Measurable residual disease correlates with disease-free survival and overall survival data for patients with acute myeloid leukemia (AML), according to results of a meta-analysis published today in JAMA Oncology. This finding supports the continued use of measurable residual disease as a surrogate end point in clinical trials.

The investigators, led by first author Nicholas Short, MD, Assistant Professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center in Houston, included oncology experts from the United States and England. Dr. Short and colleagues examined data from PubMed, Embase, and MEDLINE on 11,151 patients from January 1, 2000 to October 1, 2018. Of the 81 studies included in the analysis, 17 evaluated overall survival rates, 20 evaluated disease-free survival rates, and 44 evaluated both end points.

After five years, the estimated disease-free survival rate was 64% for patients without measurable residual disease, compared with 25% for those with measurable residual disease. Additionally, the estimated overall survival rate was 68% for patients without measurable residual disease, compared with 34% for patients with measurable residual disease. The authors concluded that measurable residual disease negativity improved disease-free survival and overall survival rates for almost all the populations observed, with an exception when measurable residual disease was assessed using cytogenetics or fluorescent in situ hybridization.

"The findings of this meta-analysis suggest that achievement of measurable residual disease negativity is associated with superior disease-free survival and overall survival in patients with AML," concluded Dr. Short and colleagues. "The value of measurable residual disease negativity appears to be consistent across age groups, AML subtypes, time of measurable residual disease assessment, specimen source, and measurable residual disease detection methods. These results support measurable residual disease status as an end point that may allow for accelerated evaluation of novel therapies in AML."

In a commentary published alongside the study in JAMA Oncology, Deepa Jeyakumar, MD, a hematologist-oncologist at Chao Comprehensive Cancer Center at the University of California Irvine, and Susan O'Brien, MD, Associate Director for Clinical Science at Chao Family Comprehensive Cancer Center, stated, "It may be beneficial to use MRD negativity as a surrogate end point for clinical trials in AML to facilitate drug development. 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… Surrogate end points may aid in getting effective therapies to patients expeditiously while still confirming the benefit of these agents with an assessment of overall survival."

For More Information

Short N, Shouhao K, Fu C, et al (2020). Association of measurable residual disease with survival outcomes in patients with acute myeloid leukemia a systematic review and meta-analysis. JAMA Oncol. [Epub ahead of print] DOI:10.1001/jamaoncol.2020.4600

Jeyakumar D & O'Brien S (2020). Minimal residual disease in acute myeloid leukemia. JAMA Oncol. [Epub ahead of print] DOI:10.1001/jamaoncol.2020.4599

Image credit: Netha Hussain. Licensed under CC BY-SA 4.0


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