Is minimal residual disease (MRD) testing routinely recommended for myeloma patients?
When Is Testing for MRD Applicable and Available?
Myeloma Expert Dr. Brian Durie discusses when testing for minimal residual disease (MRD) is applicable, and the different methods of testing available.
THE BOTTOM LINE:
Outside of clinical trials, MRD testing is not routinely recommended.
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This week’s “Ask Dr. Durie” is a recurring question for the last two or three years actually. But it’s a pressing concern for many patients. And, the question is two-part, number one, “is minimal residual disease testing routinely recommended?” And part two, “if it is recommended, what type of test is recommended to be done?”
And so, the first part of the answer is that as of now, minimal residual disease testing is actually not routinely recommended. And so, this is because, although it is extremely important to know the depth of the response and to know that depth of response at a very sensitive level, we still need to understand what we will do with that information in terms of recommendations for the patient.
And so, minimal residual disease testing means that using a bone marrow sample, one can look at, for example, one million cells using a flow cytometer for example, where the cells would pass through the cytometer. And then, one can look to see if one out of a million cells is a myeloma cell.
And so, if this testing is negative, such that there are zero, or no myeloma cells present, then we call this undetected, or mrd-zero, or negative, at this one million level is also called ten to the minus six. And so, what one frequently sees is that is that a bone marrow test was mrd-negative at this ten to the minus six level.
The question emerges though in terms of the routine use. And what one will do with this information. If, for example, the test in mrd-negative, what are we going to recommend? Do we feel confident enough that we can say, “okay, you can go ahead and stop treatment at this exact moment?” The answer to that is actually, no. We don’t currently have that high level of confidence.
And so, what about if the test is positive? If there is a little bit of remaining disease, does this mean that we need to immediately change the treatment? Or move to some much more aggressive therapy? And the answer to that is, no. Because there can be a little bit of myeloma left with ongoing treatment and this could turn out to be absolutely fine.
And so, the answer to the first part of the question is that because we don’t really know what to recommend with the test results, we do not routinely recommend that the testing be done. And so, the follow-up question, which is puzzling for many patients is, well, why are we doing this testing? And, under what circumstances are we doing it? And, the answer is that we are doing this within clinical trials. We test within clinical trials to see if one type of treatment produces more patients who are mrd-negative versus another treatment where the amount of patients or the number of patients achieving mrd-negative status is less. And this helps to tell us that one treatment might be better than another. And so, this is a very very crucial stage, in the mrd-testing - clinical trials work, we use it to compare one treatment versus another.
And so, within that setting, there are two tests that we can use, a molecular test and a flow cytometry test. The molecular test is called Next Generation Sequencing, “NGS”, and this has actually been approved for use by the FDA. The other Flow test is called, “NGF,” Next Generation Flow. Now, this is a standardized test, which is used within clinical trials as the test has not yet been approved at the FDA level.
So, the confusion is, “okay, so, if a test has been approved at the FDA level, why don’t we routinely recommend the use of the test?” And that’s because there’s this crucial next step to show, although the test is a reliable test, how do we actually use it in clinical practice? This is that crucial step that is ongoing, to understand what will be the recommendations, how do we use this information, and what will be the outcomes?
So, BOTTOM LINE, we do not yet routinely recommend testing in the clinic. However, we do basically routinely recommend it within clinical trials, so we can assess and compare treatments. And as far as the testing, we are looking at evaluating both NGS and NGF within our trials to see the relative benefits of each of those.
Dr. Brian G.M. Durie now serves as Chairman of the International Myeloma Foundation and serves on its Scientific Advisory Board. Additionally, he is Chairman of the IMF's International Myeloma Working Group, a consortium of nearly 200 myeloma experts from around the world. Dr. Durie also leads the IMF’s Black Swan Research Initiative®.