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Measuring Minimal Residual Disease in Myeloma

A recent editorial in Leukemia authored by doctors Shaji Kumar and Vincent Rajkumar of the Mayo Clinic in Rochester, MN, provides a thoughtful overview of the current status of minimal residual disease (MRD) assessment in myeloma. In it, the authors raise three questions: What are the implications of MRD negative status? What is the best method to measure it? And what do the results mean for treatment?

In introducing answers to these questions, the authors identify key aspects of the IMF's Black Swan Research Initiative, including how to interpret MRD test information; which tests to use; and most importantly, how to use MRD test results to improve outcomes and achieve true cure for myeloma patients.

From the patient perspective, it is important to realize that a negative result (MRD-Zero) does not automatically mean a patient is cured. We are learning that sustained MRD-Zero combined with other test results such as stringent CR (sCR) plus negative imaging and/or scan results can indeed translate into cure for a subset of patients. But there is more work to be done.

A Promising MRD Testing Method

The first project of the Black Swan Research investigators team was to identify the most useful MRD method. Flow cytometry was identified as a promising technique, and a collaboration was established with EuroFlow and the University of Salamanca (now also Pamplona) to develop a very sensitive, reproducible method with a computer software readout to truly standardize the method. 

Within the last year this research project has been highly successful and the results will be presented to the myeloma scientific community at a workshop in Salamanca, Spain March 20-21. Groups from the US, Europe and the Asia-Pacific region will participate in this IMF-co-sponsored meeting to reach consensus on this new flow cytometry method for MRD testing. It is strongly anticipated that this can become the new standard test which be both widely available and affordable (approximately $100 per test). The full educational rollout of this test will occur in the coming months.

Development of this test is not the end of the story, but it provides an immediate benchmark for ongoing trials and comparisons with other methods. In the short term, MRD testing is complementary to other methods of response assessment and trial endpoints.

MRD Testing and Treatment Strategies

The important third point is how to change treatment strategies based upon MRD test results? Should treatment be stopped if sustained MRD-Zero is achieved? Is it more prudent to consider some consolidation and/or maintenance therapy? Obviously trials are needed and are in development now. If MRD is positive in the setting of high-risk disease can specific back-up therapy be recommended?

Again, a key area within the BSRI is to determine the sensitivity/resistant patterns of residual clones and initiate appropriate clinical trials. Another scenario is if the residual MRD has an "MGUS signature" pattern. Interestingly, this is probably the most secure situation right now in which we can recommend careful follow-up "off therapy" to see if the residual MGUS is sustained--indicating a functional cure state.

So it is obvious that much exciting work needs to be done--BUT having a reliable test and interpretation strategies are key steps in moving the search for a cure forward!

Stay tuned on this...there is definitely much more to come soon.

Dr. Durie sincerely appreciates and reads all comments left here. However, he cannot answer specific medical questions and encourages readers to contact the trained IMF Hotline staff instead. Specific medical questions posted here will be forwarded to the IMF Hotline. Questions sent to the Hotline are answered with input from Dr. Durie and/or other scientific advisors and IMWG members as appropriate, but will not be posted here. To contact the IMF Hotline, call 800-452-CURE, toll-free in the US and Canada, or send an email to hotline@myeloma.org. Hotline hours are 9 am to 4 pm PST. Thank you.
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I want to share with all myeloma patients that my father is cancer free of myeloma
After taking Alpha lipoic acid. This natural antioxidant is cheap and effective.
He was very close to death. After two weeks of taking two capsules a day the
doctor couldn't find cancer cells on the blood test. We never told the doctor
because he never aloud any suggestion that we ask him. Well this time
my father felt that he had to take a chance. It never interfere with the doctor therapy .
You can't go wrong to try it. Best wishes to all.

Hi Omar,

Good to know about your dad. Can you tell me what stage of Myeloma was your dad in and what treatment he was undergoing? Is it okay to still take Alpha lipoic acid if Velcade is already used for treatment?

Is it possible for anyone (aka me) to read the full Kumar-Rajkumar editorial?

MRD is interesting but to the layman what is the definition ? I can guess that there is an indication that Multiple Myeloma, which my wife has, no longer shows as a cancer in a treated patient. But there somehow lies the cancer in a somewhat dormant state. So, though the there is no apparent indication of MM Cancer, there lies some residual low level cancer which can be detected through a special test.
Please let me know if this is correct and how MRD is detected in a patient.

Thank You

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