In Myeloma, How Is Minimal Residual Disease (MRD) Measured?

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Dr. Robert Orlowski from MD Anderson Cancer Center and Dr. Paul Richardson from Dana-Farber Cancer Institute discuss minimal residual disease (MRD). The experts explain what MRD is, how it’s measured and what the test means related to prognosis. Both Dr. Richardson and Dr. Orlowski share specifics about how this test is used as well as other effective modalities that may be used in the future. 

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Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Jack Aiello:

Dr. Richardson, I’ve heard about even more sophisticated ways of testing that go by the name of minimum residual disease, or MRD.  Can you say a little bit about where we are in MRD testing these days? And can patients ask for that, or is that still to be determined? 

Dr. Richardson:

Well, I think great question, Jack.  I think MRD is a goal that we’ve now finally been able to grasp, because of the success of our treatments. And I think that it’s a very important end point because, as people live longer with this disease, clinical trials where we’re looking for clinical benefit that can be of the highest standard that can also allow our regulatory groups, such as the FDA, to approve drugs, if you’re looking at older end points like survival, obviously, they’re key.

But at the same time, you may have to wait a long time, which is great news for our patients.  So now, we need surrogates that tell us we’re going to do well.  The original surrogate was progression-free survival.  And that certainly works in the relapse setting.  For example, if disease relapses, progression-free survival has consistently been shown to correlate with overall survival.  But as we touched on earlier with the transplant question, just because you see a progression-free survival benefit doesn’t necessarily mean you’ll get an overall survival benefit as in transplant.

And that’s actually a very interesting point, because all of the studies we’ve had so far did not show survival benefit to transplant. They show progression-free survival benefit. So then the question is what do you do about other surrogates? And so MRD has emerged as a very provocative and hopefully very useful tool for the future. 

And what it involves is ascertaining a minimal disease state. And that doesn’t just mean disappearance of the protein. It means disappearance by immunofixation. And it means the absence of clonal myeloma cells in the marrow. and how do you assess that. And finally, a second piece to it is also imaging. Where [do] MRI and PET CT, as Bob talked about earlier, help us understand where the disease state is? So true MRD negativity now is defined not just by cellular characteristics in the bone marrow and by chemistry but also by imaging showing no evidence of disease elsewhere.  So this is evolving, because, obviously, that’s not an easy thing to do for everyone. 

In clinical practice, what I utilize is marrow, imaging and, obviously, by chemistry to ascertain stringent complete response.  True MRD testing probably, I think it’s fair to say, Bob, is really the remit of clinical trials right now.  I think that’s reasonable.  And I think for going forward, for patients outside of clinical trials, a sort of useful surrogate for MRD would be stringent CR. Does that seem fair, Bob?

Dr. Orlowski:     

I think that’s right.  One of the ways, though, that we can, and probably both of us do this, measure MRD from a bone marrow is that when the pathology doctors look at the bone marrow, they can tell you that you have, let’s say, 3 percent plasma cells. And that can be okay if they’re all normal plasma cells. But if that’s 3 percent myeloma-type plasma cells, that has a different implication. And there’s a test called flow cytometry, which is kind of like a fingerprinting of the plasma cells that can be done, which lets the doctors determine whether those plasma cells are normal or abnormal. 

We know that people that have normal plasma cells do better in terms of time and remission than people who have abnormal plasma cells.

We don’t yet know whether we should treat the ones with abnormal plasma cells differently. But it is a way for you and your doctor to get a better idea of what your prognosis is, at least. And so from that perspective, it’s still something I think we should be offering to people, even though we don’t know as much about the tests as we would like to. And there’s another test that is done sometimes on blood, which is to look for DNA from the myeloma cells, which can be actually found in the serum and in the plasma.  This is another test where, if you’re negative on that, you probably have a longer time in remission than if you’re positive on that. 

That one isn’t yet routinely available.  But I think it’s important for people to know about these, because we’ll probably be using them more often in the future. 

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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Page last updated on September 30, 2015