If you have measurable disease, is there a reason to consider MRD testing?

If you have measurable disease, is there a reason to consider MRD testing?

So a common question in the clinical setting is also, is there a reason to do a bone marrow based MRD test?

Even if I have a protein? So I try to highlight on the fact that there is a discordance between the biopsy and the protein in the blood. In the modern era of treating the disease. So the answer is yes. There could be reasons to do a biopsy even if there is a protein. And the reason is that the proteins that are made by myeloma cells, they last longer in the blood than we previously thought.

So if you have someone who receives a very effective therapy, such as CAR-T Cell therapy or a combination therapy, let's say with four drugs, after one or two months, if you do a biopsy, the patient could be. MRD Negative. But that still is a lot of protein in the blood. That doesn't mean that the cells are still there making the protein.

That protein was made by the cells that are no longer in the body. So if you follow that patient over time, you could see that these protein levels keep on going down and it could take several months. It could even take. In my experience, in extreme cases, up to a year for these proteins to fully clear, I think the guidelines are a little bit behind what happens because there are so many new therapies in the field.

So on a practical note, I think patients are

newly diagnosed if they are receiving, say, four cycles of therapy and they are going for collection of stem cells.

It would make sense to do a biopsy and check for MRD at that point. That is endorsed also by the NCCN guideline and is therefore also reimbursed by insurance or CMS for Medicare.

If the patient goes for a transplant or the patient gets another few cycles, four more cycles with a delayed transplant to do a biopsy again would be justified and supported by guidelines. And this could be done independent of what the proteins really show. Statistically speaking, in the individual who has no protein in the blood is of course more likely to be MRD negative in the bone marrow than the person who has a little bit protein.

But there are individual that have protein for the reason I just gave and they still are MRD negative. And because every person is unique, you cannot rely on probabilities. You need to know for yourself. So therefore, I think it makes sense to do it this way.

So there's a number of reasons why you might want to do MRD testing, as well as looking at the disease under the microscope. So there are many situations where you could have still an M spike or a light chain present. And all of this plasma cells may be gone from the bone marrow. That happens in a significant proportion of cases and vice versa.

So comparing the both tests are good, but MRD testing is not really about one and done at any specific time. It's about monitoring your disease over time. And so if you go negative, great, you should still have the MRD test in the next year because if you're still negative, then that's a stable molecular response. That's great. But what if you become positive?

What do you do then? And so then you can go from undetectable one cell in ten to the four You have one cell in 10,000, one cell in a thousand, one in 100. And you still wouldn't see it if you looked down the microscope. So you can pick up patients relapsing over time. And surely now is the time when we should be treating people before they relapse with holes in the bones or kidney damage.

So the monitoring is becoming a critical component of myeloma care.