BETA - Can MRD testing be done on a blood sample instead of a bone marrow sample in multiple myeloma?

00:00:06:14 - 00:00:39:13 Unknown In this Health Tree video, we explore the emerging field of blood based MRD, or measurable residual disease testing in multiple myeloma. Learn what blood based MRD testing is, how it works, and why researchers are excited about its potential to detect tiny amounts of remaining myeloma cells with a simple blood sample. We'll discuss how these tests are performed, what they may reveal about treatment response and disease monitoring, and how they compare with traditional bone marrow based MRD testing. 00:00:39:15 - 00:00:52:03 Unknown We'll also examine whether blood based MRD testing is currently approved for routine clinical use or still considered investigational, and what role it may play in the future of personalized myeloma care. 00:00:52:05 - 00:00:55:04 Unknown Why is there excitement around blood based MRD testing? 00:00:55:05 - 00:01:11:02 Unknown there's there's a lot of excitement around blood based testing. And really the biggest advantage is that it uses a blood sample, not a bone marrow based sample, to look for low levels of disease. 00:01:11:02 - 00:01:39:13 Unknown And so that has a huge advantage. You know, bone marrow sampling is not convenient. It's it's painful. It's an invasive technique. And so taking a blood sample is much easier on the patient. And that allows for more frequent sampling. So you can measure the patient monitor the patient more closely more frequently with a blood based test. 00:01:39:14 - 00:01:43:17 Unknown Our blood based MRD tests for multiple myeloma. Consider the standard of care. 00:01:43:17 - 00:02:11:15 Unknown So these are still kind of being evaluated. We're still trying to see whether these tests can detect disease at the same level of sensitivity as the bone marrow tests, and whether the blood based assays give us the same information, or whether they predict patient outcome, the same way that bone marrow based MRD tests predict outcome. 00:02:11:15 - 00:02:20:05 Unknown And so that work is still being done. We need clinical trials to sort of answer those questions, but those are kind of in progress. 00:02:20:05 - 00:02:23:12 Unknown What blood based MRD technologies are being explored in myeloma. 00:02:23:14 - 00:02:49:07 Unknown So we are starting to see some of these techniques primarily just in research studies. And there's a lot of different blood based MRD techniques that are being evaluated. So kind of the main things that are being looked at, the mass spectrometry in the blood to measure very low levels of the monoclonal protein. 00:02:49:07 - 00:03:25:05 Unknown So this is tracking the protein that's secreted by myeloma cells, and the same protein that gets measured in routine blood tests. Serum protein electrophoresis immuno fixation. Mass spec just provides a very sensitive way to detect low levels of this protein. There's following circulating tumor DNA with different methods. One of them is next generation sequencing. So sequencing methods to look for DNA that's coming from the myeloma cells. 00:03:25:07 - 00:03:48:06 Unknown So the cells can shed DNA into the blood. And then we can also look for myeloma myeloma cells themselves that circulate in the blood using say flow cytometry or next generation sequencing, similar to the technique that's being used to analyze bone marrow samples. 00:03:48:06 - 00:04:01:04 Unknown How is mass spectrometry being used to evaluate measurable residual disease MRD status in multiple myeloma, and how does IT sensitivity compare with traditional serum protein electrophoresis? ESP. 00:04:01:06 - 00:04:06:21 Unknown the monoclonal protein is a really important biomarker that's monitored in blood. 00:04:06:22 - 00:04:20:04 Unknown In multiple myeloma. Cancerous plasma cells make large amounts of an abnormal antibody called a monoclonal protein or M protein. Think of it as a signature protein produced by the myeloma cells. 00:04:20:07 - 00:04:32:20 Unknown Normally healthy plasma cells create many different antibodies to help fight infections in myeloma. However, one group of abnormal plasma cells copies itself over and over, producing large amounts of the same exact antibody. 00:04:32:21 - 00:04:47:21 Unknown Monoclonal protein is an important biomarker because it helps doctors track how much myeloma is present in the body. Higher levels may indicate more active disease, while falling levels after treatment usually suggests the therapy is working. 00:04:47:21 - 00:05:14:23 Unknown So it's traditionally measured by serum protein electrophoresis and immuno fixation. Those techniques basically separate proteins based on their charge. And we can identify the monoclonal protein because it has a specific charge that we can look at on the s Pep mass spec is a little bit different in that it separates proteins based on their mass. 00:05:14:23 - 00:05:46:07 Unknown And so what's really useful about mass spectrometry is it gives us really good specificity. So we can measure the mass of the patient's monoclonal protein. And so if we know that ahead of time, if we measure it up front, we can look for that mass in later samples after the patient's been treated and be able to detect really low levels and tell if that mass is still present in the sample. 00:05:46:09 - 00:06:02:01 Unknown So in terms of sensitivity, there's there's a couple different methods that are anywhere from 10 to 1000 times more sensitive than immuno fixation at measuring that monoclonal protein. 00:06:02:01 - 00:06:10:18 Unknown How does the sensitivity of using mass spectrometry to detect minimal residual disease compare to the currently approved myeloma bone marrow based technologies? 00:06:10:18 - 00:06:30:03 Unknown it's a little bit tricky to compare because it's a little bit like comparing apples to oranges, because you're measuring the protein that's secreted by the cell in the mass spec test versus our current bone marrow assays are actually some of them are measuring the myeloma myeloma cells themselves. 00:06:30:05 - 00:07:03:21 Unknown But when we compare the two techniques directly, some of the mass spec assays are about equivalent to ten to the minus five, ten to the minus six. And in some cases, we're still able to detect the M protein even when the patient's negative in the bone marrow at ten to the minus six. So in some cases, the mass specs being a little bit more sensitive in detecting M protein compared to being able to detect the cell in the bone marrow. 00:07:03:21 - 00:07:08:00 Unknown Could monoclonal protein be present in the blood even after the myeloma cells die? 00:07:08:00 - 00:07:15:18 Unknown that's a really good question. So yeah. So that's why we want to compare these new blood based techniques to bone marrow. 00:07:15:18 - 00:07:47:01 Unknown And also compare how these blood based techniques predict outcome. Because there's the potential for false positives, especially when we're measuring the protein in blood. Because for some monoclonal proteins, especially IgG isotopes, they take a while to be cleared by the body. So they'll circulate in the body even after the myeloma cells have been killed. So the protein can stick around. 00:07:47:02 - 00:08:01:12 Unknown So usually early in therapy you'll see the bone marrow become negative. But the mass spec tests still be positive. And a lot of times it's due to just this delayed clearance of the M protein. 00:08:01:12 - 00:08:06:06 Unknown How is the technique being used to detect minimal measurable residual disease in the blood? 00:08:06:07 - 00:08:17:11 Unknown the test is looking for DNA. So it's using sequencing to identify DNA that's 00:08:16:13 - 00:08:17:13 Unknown specific to 00:08:17:13 - 00:08:19:02 Unknown to the myeloma cell. 00:08:19:02 - 00:08:25:05 Unknown Are there specific groups of multiple myeloma patients for whom blood based MRD testing may not be an ideal option? 00:08:25:07 - 00:08:42:02 Unknown Because the blood sample we discussed now is minute amounts of light chains and monoclonal components. If the cancer cells have stopped producing them or produces them to such a small amount that it's not detectable, you can be negative there. 00:08:42:04 - 00:08:51:08 Unknown let's say you have that doesn't produce anything. Then you won't see anything no matter how how many cells you have left in the body. So that's that's the reason 00:08:51:12 - 00:08:56:22 Unknown non secretary is a very easy example of this. But it's also about lo secretary 00:08:56:23 - 00:09:06:05 Unknown when you have quite a few myeloma cells left in your body and they don't secrete that much, there's a, there's a limit to the detection level in the blood. 00:09:06:06 - 00:09:17:03 Unknown But that will also, as everything else will probably also increase, we will increase the sensitivity of those samples also, I guess as time goes by. 00:09:17:03 - 00:09:21:07 Unknown What should myeloma patients know about the currently available blood based MRD tests? 00:09:21:09 - 00:09:27:07 Unknown there are blood based MRD tests that are commercially available to patients. 00:09:27:09 - 00:09:58:02 Unknown this means even if they're not FDA approved, they can be available as what's called a laboratory developed test. So the individual lab has done validation studies to to understand how that method works and how it performs analytically. And there might be some clinical utility data about it, but I would say the blood based MRD testing is still research. 00:09:58:03 - 00:10:29:22 Unknown We're still trying to understand how to use that information clinically, what that means, and how to make treatment decisions based on blood based testing. We still don't really know what it means to say have an M protein detected at very, very low levels. If that means the patient still has disease that needs to be treated. And so those studies are still being done, 00:10:29:22 - 00:10:40:02 Unknown we still need like a lot more information to get to the level of understanding that we have with the currently accepted bone marrow MRD testing, 00:10:40:03 - 00:10:45:06 Unknown Why are blood based MRD tests being used more frequently in other blood cancers and not myeloma? 00:10:45:09 - 00:10:48:22 Unknown because myeloma really lives in the bone marrow. 00:10:48:22 - 00:11:27:22 Unknown And most of our studies, most of our understanding about testing has been done with bone marrow based tests and treatment decisions in the clinical trials, with treatment decisions based on MRD testing. Those are all all been based on bone marrow based MRD tests. There's not yet that same level of information for blood based. So we don't yet know how the blood based results compare and perform relative to the bone. 00:11:27:22 - 00:11:52:05 Unknown The currently accepted bone marrow test, the the disease because it lives in the bone marrow and is not as the cells don't really go into circulation. Instead, where a lot of the the blood based MRI testing relies on biomarkers, right. Things that are secreted by the cells, either the protein 00:11:52:06 - 00:11:56:11 Unknown those tend to be less concentrated in circulation. 00:11:56:11 - 00:12:04:15 Unknown And so, the test in blood might be negative when you still have disease present in the marrow. 00:12:04:15 - 00:12:08:20 Unknown How could blood based MRD tests still be useful in multiple myeloma at this point? 00:12:08:20 - 00:12:28:15 Unknown so at least in some of the early clinical trials, what we're seeing is when patients are negative by the bone marrow MRD testing and the blood based testing, they tend to do better than patients who are negative by just one of the techniques. 00:12:28:15 - 00:12:34:14 Unknown So it does add some information. If both bone marrow and blood are negative, 00:12:34:14 - 00:12:40:16 Unknown ongoing trials right now looking at how we could use the blood based information. 00:12:40:18 - 00:12:47:15 Unknown certain settings when, say, when a patient is negative in the bone marrow 00:12:47:19 - 00:13:01:00 Unknown the trial is evaluating whether they can reduce therapy or even stop therapy, having something that monitors the patients more closely, more frequently, more frequent samples, that's useful. 00:13:01:00 - 00:13:12:01 Unknown And I think that's some something that's being explored in current clinical trials. 00:13:07:14 - 00:13:12:01 Unknown Can blood based MRD test be used to detect relapse sooner than the traditional s Pep? 00:13:12:03 - 00:13:28:02 Unknown Yeah. So what we're seeing, for example, the mass spectrometry test, we can see the M protein concentration increase obviously much earlier than we can with the traditional electrophoresis techniques that are still 00:13:28:02 - 00:13:36:04 Unknown undetectable at that point. And so they are predicting earlier relapse because we can see 00:13:36:06 - 00:13:38:16 Unknown biomarker increase in concentration. 00:13:38:16 - 00:13:43:03 Unknown What are the current criteria for a multiple myeloma patient to be considered MRD negative? 00:13:43:03 - 00:14:01:01 Unknown currently in my Loma you have to do the bone marrow based testing either by 00:13:48:19 - 00:14:01:03 Unknown next generation sequencing or next generation flow at a minimum sensitivity of ten to the minus five in order to be considered mid negative. 00:14:01:03 - 00:14:05:10 Unknown What does the future look like for blood based MRD tests in multiple myeloma? 00:14:05:12 - 00:14:27:10 Unknown the future I think we are going to see the blood based tests be accepted and be used clinically. I think they're going to help reduce the amount of bone marrow testing that is required. I don't think it's going to completely replace the bone marrow testing because, again, myeloma is a disease of the bone marrow. 00:14:27:10 - 00:14:27:20 Unknown And there's 00:14:28:02 - 00:14:36:21 Unknown information that we can get with a bone marrow sample about the cells that you can't get with some of the blood based tests. 00:14:36:23 - 00:14:43:16 Unknown think it's going to really help monitor patients more frequently and 00:14:43:18 - 00:14:52:19 Unknown help really reduce the amount of bone marrow sampling that is needed. 00:14:48:02 - 00:14:52:20 Unknown What are your final thoughts on blood based MRD tests for multiple myeloma in 2026? 00:14:52:21 - 00:14:58:10 Unknown which myeloma patients know about blood based MRD testing in 2026. 00:14:58:10 - 00:15:17:07 Unknown So blood based testing in my Loma is still an area of research. We're still trying to understand how and when to use these techniques appropriately. But there are things that you can do to think about blood based testing and 00:15:17:07 - 00:15:33:08 Unknown get involved in what based MRD testing. For some of the tests, it's really important to have a baseline sample so we can characterize either the monoclonal protein like the mass of the monoclonal protein if you're talking about mass spectrometry or sequencing. 00:15:33:08 - 00:15:40:16 Unknown And so those things need to be thought about early and upfront when disease is still detectable. 00:15:40:18 - 00:15:52:17 Unknown getting baseline on these assays is important. Or perhaps thinking about banking a blood sample, a serum sample for these tests to be done later 00:15:52:18 - 00:16:08:04 Unknown Blood based MRD testing is an exciting emerging tool that may help make myeloma monitoring less invasive and more personalized. As research continues, it could play an important role in guiding treatment decisions and tracking disease over time.