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.
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