Measurable residual disease shows strong potential as an early indicator of survival in patients with acute myeloid leukemia

(Press-News.org) (ORLANDO, Dec. 6, 2025) Sensitive tests designed to detect very small numbers of remaining leukemia cells after treatment, known as measurable residual disease (MRD), may provide an early and reliable indicator of long-term outcomes for patients with acute myeloid leukemia (AML), according to a new study from the HARMONY Alliance.

The study is the first to evaluate MRD as a potential measure of treatment efficacy and outcome prediction in the context of AML. The results suggest that MRD could help refine how physicians assess treatment response and personalize post-remission care. The findings may also help regulators determine whether MRD can serve as an intermediate endpoint for clinical trials of new AML therapies, providing an earlier signal of treatment benefit.

AML is a cancer that occurs in the bone marrow, causing an overproduction of abnormal white blood cells and impeding the production of healthy blood cells. MRD is an established biomarker in several blood cancers and is increasingly used to guide therapy. The U.S. Food and Drug Administration (FDA) has already accepted MRD as a surrogate endpoint in clinical trials for multiple myeloma, which can help speed regulatory approvals for new therapies since MRD can typically be assessed years earlier than survival outcomes. However, the FDA has not approved MRD as a surrogate endpoint for AML.

To assess the reliability of MRD as an early predictor of survival for AML at the individual and trial levels, researchers analyzed data from 1,858 patients who underwent MRD tests as part of their participation in seven prospective clinical trials conducted by four European cooperative groups. At the individual-patient level, those who tested MRD-positive after two cycles of intensive chemotherapy were less than half as likely to survive as those who were MRD-negative. This strong association held true regardless of the assigned study arm or MRD testing method.

“The individual-level association is pretty striking – MRD positivity remains an independent predictor of worse outcomes,” said Jesse Tettero, MD, PhD, who led the research while at Amsterdam University Medical Center Department of Hematology in the Netherlands. “It provides stronger prognostic information than any single genetic or molecular marker we currently use. The association was very consistent, even after adjusting for other clinical factors, which really confirms the patient-level link between MRD and survival.”

At the trial level, the analysis showed that treatment effects on MRD closely mirrored those on overall survival, particularly among patients who did not receive a hematopoietic cell transplant (HCT). The correlation between MRD improvement and survival benefit was high, but the confidence interval for this association fell below the study’s predefined threshold for this endpoint. In addition, the relatively small number of available randomized trials limited the precision of this estimate.

“For the trial-level surrogacy, the data for non-transplanted patients show a strong correlation, but caution is warranted due to the number of trials. Trial-level surrogacy is a very high bar to reach,” said Dr. Tettero.

Regulators could consider accepting MRD as an intermediate endpoint rather than a full endpoint. In this case, data on MRD status could be used as a basis for provisional approval while the study continues and survival data matures. “This could speed AML drug development without compromising the quality of evidence. That may be a reasonable implementation,” said Dr. Tettero.

The results revealed HCT could modify the relationship between MRD and long-term outcomes. MRD is typically measured shortly after a patient completes initial treatments – a point in time that is before patients would receive a transplant – yet HCT strongly affects outcomes because it is a curative therapy in most cases, influencing the trial-level surrogacy.

Researchers noted that not all MRD tests are equal. High-volume reference centers using standardized methods produce the most reliable results, while decentralized, low-volume testing can be less consistent.

“The quality of MRD testing really depends on where and how it’s done. Centralized, experienced laboratories deliver accurate and reproducible results, which are essential if MRD is to be used for clinical or regulatory decisions. I think the field has really developed and matured, so people are becoming more interested in using MRD,” said Dr. Tettero.

The study was conducted within the HARMONY Alliance, a European public-private partnership funded by the European Union.

Jesse Tettero, MD, of Virginia Tech FBRI Cancer Research Center, will present this study on Saturday, December 6, 2025, at 4:00 p.m. Eastern time in Valencia Room W415A of the Orange County Convention Center.

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The American Society of Hematology (ASH) (hematology.org) is the world’s largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. Since 1958, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. Join the #Fight4Hematology by visiting hematology.org/fight4hematology.

The Blood journals (https://ashpublications.org/journals) are the premier source for basic, translational, and clinical hematologic research. The Blood journals publish more peer-reviewed hematology research than any other academic journals worldwide.

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