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Minimal residual disease measures not yet impactful for AML patients


 

EXPERT ANALYSIS AT NCCN HEMATOLOGIC MALIGNANCIES CONGRESS 

 

– Routine testing for minimal residual disease is probably not of value in acute myeloid leukemia, as there is no evidence that changing treatment based on MRD status currently makes a difference in patient outcomes, experts said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.

“If we find minimal residual disease, we don’t always have a better therapy to offer our patients,” Jessica Altman, MD, associate professor of hematology and oncology at the Northwestern University Feinberg School of Medicine, said.

Beyond that therapeutic reality, there are no clear guidelines and standards for MRD testing. The optimal timing for MRD testing and a standard threshold for an MRD classification are not yet established, she said.

“Having MRD is bad, not having it is better,” Richard Stone, MD, PhD, clinical director of the adult leukemia program at the Dana-Farber Cancer Institute, said. The problem in AML, he said, is, “So?” There is no reliable “MRD eraser” in AML, he said. Until then, there is not much point in knowing whether a patient is MRD positive or not.

A recent survey conducted by researchers at Moffitt Cancer Center, Tampa, addressed MRD testing at 13 major cancer centers. While most centers reported that they test for MRD, many physicians said that they are unsure about what to do with the results.

A 2013 study by the HOVON group found that patients who were in complete remission but MRD positive after their first course of therapy, subsequently became MRD negative after their second course of therapy. But the second regimen would not have been different based on knowledge of MRD status, according to the HOVON/SAKK AML 42A study (J Clin Oncol. 2013; 31:3889-97).

The AML community is awaiting guidelines on MRD use from the NCCN and other groups, Dr. Altman said. An option for using NPM1 mutations to assess MRD should be available soon, and could be an improvement on existing options (N Engl J Med 2016; 374:422-33).

Given the treatment limitations, knowing about MRD status can have a negative mental toll on patients, Dr. Stone said. “I would not underplay the psychological burden.” Nevertheless, MRD should be measured in clinical trials, and it could be a valuable surrogate marker by which to compare drug efficacy.

One of the biggest hopes is that MRD status could eventually be useful in determining the need for allogeneic stem cell transplant in patients deemed intermediate risk, Dr. Altman said. “I think we are finally on the brink of this being actionable.”

Dr. Altman reports financial relationships with Astellas, Bristol-Myers Squibb, Celgene, Janssen, Novartis, and Syros. Dr. Stone reports financial relationships with AbbVie, Actinium, Agios, Amgen and many other companies.

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