Is MRD testing a standard of care?

Is MRD testing a standard of care where is MRD testing done.

The good question is if MRD is a standard of care test or is a test that is still considered investigational. And the answer to that is not straightforward and probably a little bit controversial. There is one test that is endorsed by the FDA is the clonoSEQ next generation sequencing test. There are several laboratories around the country that also offer a next generation flow.

And how we use that in clinic varies tremendously. I think I see very little use outside myeloma centers of excellence with out outside myeloma specialized clinics, although, you know, but on those centers is becoming, you know, more and more common. Many of us use that as mainstream very much like we use any other marrow based test.

MRD testing is considered standard of care in multiple myeloma. Currently, it can be tested several different ways, so it can be tested at local labs and in most most commonly at major academic or myeloma centers, where they can do in-house testing called flow cytometry, where basically the testing involves checking

the cells that are collected through a bone marrow aspirate and basically gating them through a machine and checking enough of these cells to see how much how many of them potentially could represent myeloma or residual myeloma.

And so that's one potential way

to check for minimal residual disease. Or MRD negativity locally at ones clinic or hospital. The other sort of more

centralized way to check for MRD negativity is through a next generation sequencing. This is more of a centralized test. It's actually a send out test that can be sent to a company called Adaptive Biotechnologies, where it's a test called ClonoSEQ, where basically DNA sequencing is used to track clones of residual myeloma that might be present from the patient's original myeloma clone.

And so that's another way that if your local hospital or clinic doesn't have that testing available, it can be sent as a send out test by your your physician to to test for MRD negativity

MRD testing.

is most useful when a patient's myeloma is in a deep response, typically at least a very good partial response or better.

And so MRD testing is not very useful if a patients is getting a bone marrow relapse, for instance, or is first diagnosed, because we would expect that to be a lot of myeloma in the bone marrow anyways and that have less relevance. But for instance, if a patient has completed their initial therapy for multiple myeloma and is getting a bone marrow biopsy just before undergoing stem cell transplant, or for instance, a patient that has undergone a stem cell transplant and has is undergoing a bone marrow biopsy to assess response, those would be an important time points to check for MRD negativity if the bone marrow.

Is being done in the maintenance setting and to check to see if the patient responded well to therapy. That may also be a very good time and important time. Check for MRD Negativity and not only just for MRD negativity, but another important endpoint is sustained MRD negativity. So having one MRD negative test is certainly nice, but having multiple MRD negative tests and when we call sustained MRD negativity is a much more powerful tool to to prognosticate myeloma, disease control and actually survival in the future.

Think MRD testing is not a uniformly available standard of care for myeloma right now. I think it's moving in that direction. But I think that whether it becomes the an absolute standard of care is a function of both the data and availability and accessibility. And I think there are FDA approved tests such as the clonoseq test, which is a next gen sequencing test from adaptive that does looks at MRD testing by the next gen sequencing method, there are flow cytometric methods that people can do in-house and also at other companies that can look at whether people have MRD or not.

I think that right now the guidelines don’t necessarily say that everyone should get MRD testing and I think the data really are maturing to to really tell us whether that's absolutely useful to everyone all of the time. I think the people where it's most relevant are people who have a deep remission or a complete remission where you're like, Look, I don't see much evidence by standard testing methods that they have active disease.

Why don't I look and see if I can find evidence of disease by MRD testing? And there are studies that have shown us that different levels of MRD have different implications for long term outcomes. However. Is it ready for prime time as the saying goes? And can I necessarily make decisions now based on what the MRD level is for someone?

This is a bit challenging of a case to make. There are many numerous trials looking at MRD directed interventions which would hopefully give us a better idea in the near future.

That is a great question. So MRD testing is now approved by the FDA, right? So there is a platform called Adaptive, which

is used for MRD testing. There are other tests that institutions have the accuracy and sensitivity and reproducibility of those assays vary. But you know, a lot of institutions have their own assays through which they can detect.

MRD. So at most at all, I mean, at all academic institutions, there will be a way to check MRD and that way might vary between institutions, including how they're measuring MRD and how accurate that is. So I would say that it is approved. It is fairly standard. I guess. Is it standard of care is a bit of a controversial question.

It definitely is information that's very helpful. It what's less clear is can this information be used to make decisions in the clinic? And we have trials ongoing that will help. But as of today,

for a lot of situations, we don't really know whether to change treatment based on MRD alone. Right. Should we do more treatment if somebody still is MRD positive, should we stop treatment of somebody is MRD negative?

These are questions that we don't have the answers to. So it is standard of care and it is reimbursable and it is helpful information, but we often don't know what to do with that information. That is one of the issues with MRD. But that will change. It's a matter of time and then soon we'll be able to have actionable information and we'll be able to make decisions based on MRD.

But we're a few years from that.