MRD Testing for Myeloma: What Is It, Who Should Be Tested and Why?

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Topics include: Treatments and Understanding

What is MRD? Who should be tested? From the Myeloma 2016 meeting in Boston, Dr. Ola Landgren from Memorial Sloan Kettering Cancer Center explains MRD and what patients should be tested. He goes on to discuss how MRD and other diagnostic tests are being used by doctors in myeloma care, as well as updated guidelines for testing provided by the International Myeloma Working Group (IWMG).

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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. 

Tamara Lobban-Jones:

Hello and welcome, I’m Tamara Lobban-Jones. Joining us from the Myeloma 2016 meeting being held in Boston is Dr. Ola Landgren. Dr. Ola Landgren is Chief of Myeloma Service at Memorial Sloan Kettering Cancer Center. Dr. Landgren, can you tell us, what is MRD testing?

Dr. Landgren:     

So minimal residual disease detection (MRD detection) has been around for several years in clinical medicine. In leukemia, it has been going on for more than 10 years. I think the disease, chronic myeloid leukemia (CML) as probably the poster child disease for MRD testing really has found its place in clinical practice. It basically is a way to look if there is any disease left behind beyond the standard measures. That's simply what it is. For example, in CML it has been found that if you keep patients on therapy and they reach MRD negativity and they do that for an extended period of time, therapy can be safely stopped in a large proportion of patients. 

So it could be a step in the direction of cure. This is what we are trying to do in myeloma.

Tamara Lobban-Jones: 

Okay, Dr. Landgren, so at what point should patients can walk into a medical center and ask for an MRD test? Or is this a questions they should already be asking?

Dr. Landgren:     

So MRD testing in myeloma was developed about 15 years ago, and it started in small groups actually in Europe. The UK was one of the early sites, and also in Spain they developed, and they're having other groups as well. At that point, the therapists were not as good. So now we are at the point where there are very effective not so toxic drugs. So the timing is on for anything, so these new drugs combined with MRD testing and MRD testing being updated, that is now available in many places.

All the drugs are not available everywhere in the whole world. So patients can probably ask their doctor, do you conduct MRD testing? What types of drugs do you use? Different countries have access to different drugs. At our institution, I have enforced every patient that has come to our institution that reached a complete response with the conventional criteria, that patient is now being tested for MRD status as part of our clinical pipeline. So you don't need to be on a clinical trial. 

I do think that many institutions for right now have MRD testing as part of clinical trials, but I foresee in the coming few years that it's going to become standard. I think one of the drivers for that is going to be the fact of the International Myeloma Working Group guideline. They document that it's being used to assess treatment response that will include MRD testing in the new version that's anticipated to come out actually in 2016.

Tamara Lobban-Jones:

Just to follow up on that, will MRD testing be done via flow or sequencing?  

Dr. Landgren:     

At this time, there is a lot of discussion in the multiple myeloma field which technology is the better one. Flow cytometry sequencing—sequencing looks at the genetic content, or you could even do, for example, imaging with PET-CTs. I think looking at the data, looking across the studies—the two technologies that have been done are flow cytometry-based testing of the bone marrow and the sequencing of tumor cells in the bone marrow. Both these technologies have strengths and weaknesses.

Flow cytometry uses quite old technology. Flow cytometry machines have been around for very many years, and they are available at most institutions. Antibodies that are being used to label the cells, and then you put the sample with these antibodies into the flow machine. How that should be done and how it actually is being done varies quite a lot across different institutions. So on a practical note and what testing with flow cytometry can have very good sensitivity, but they can also be less good sensitivity depending on how it's set up. 

There's clearly a need to standardize that, and I mentioned to you before that we have just conducted a survey showing that there is a very wide range in terms of quality and sensitivity. For sequencing, that's an easier test to do. It's much more independent of the person who runs the test. The problem with that test is that there is no available technology that hospitals and clinics can purchase running their own facility at this point. So you have to send out the samples to very few sites that are currently doing it worldwide.

I do foresee in the coming year or two that these technologies will become available, and I think that is going to drive all the development.  

Tamara Lobban-Jones:   

You've got all this information from where the sequencing offers are. What are doctors going to do with this? 

Dr. Landgren:     

So for right now, there is a lot of confusion, because the technologies have these strengths and weaknesses, and which technology shall you use? I do think as the technology emerges and becomes mature, for example, if sequencing becomes the standard, which I personally think it will, then technology is taken care of. Also, as drugs are coming into all places around the world and becoming available, I think that will also put pressure on the new drugs becoming available. There are a lot of drugs that are currently in review at the regulatory agencies around the world at this point. 

I think in the coming year or two we will see major upgrades in terms of availability globally. I would like to mention that we just reviewed an update on a number of patients with myeloma. This year, there were 104,000 patients diagnosed with myeloma worldwide. All these patients should be given access to these modern drugs. So I think with the new technologies—with the new measuring, the MRD testing, and with the new drugs—that's what puts pressure. 

Then all the information needs to go out to physicians, and I think patients will play an important role asking the doctor are you following the most up-to-date guidelines? 

Tamara Lobban-Jones:   

Dr. Landgren, related to diagnostics, what testing should patients have so that myeloma care can stay optimized?

Dr. Landgren:     

So there are guidelines how patients that present with their symptoms or lab abnormalities that are suspicious of myeloma. All those individuals should be worked up. The International Myeloma Working Group has played an important role trying to harmonize and come up with guidelines that doctors have agreed upon around the world. So in a simple way to summarize, they include blood tests. That would be the first step. Also, urine tests should be done in some instances, but blood test is really the first step. 

If patients have symptoms such as pain or repeated infections, imaging would be something to consider. If this blood test and/or the imaging would capture certain abnormalities, a bone marrow test would be required. Bone marrow tests include multiple components when it comes to the analysis of the sample. There is both a core biopsy that's being used for so-called immunohistochemistry when the sample is reviewed under the microscope. Also, there is the aspirate that's being reviewed both usually with the flow cytometry machine and also can be used to do characterization genetically of the disease that has a prognostic impact. Those are tests that are clearly spelled out in this guideline, and doctors who are unsure about it should go back online and pull out these documents. Patients can read about it as well. It's available online.

Tamara Lobban-Jones:   

Dr. Ola Landgren from Memorial Sloan Kettering Cancer Center, thank you for your insights and your knowledge and thank you for being with us today. 

Dr. Landgren:     

Thank you.

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 May 11, 2016