Can molecular testing of the blood as opposed to the bone marrow be used to determine MRD status?

Can we use molecular testing in the peripheral blood instead of the bone marrow for prognosis? That's a great question. We don't have yet the technology to have a guarantee that this will tell us how well a patient will do. A lot of companies and investigators are trying to find that special assay that allows us to be able to detect malignant plasma cells and then use that information for prognosis from the blood.

Because as most people know, having a bone marrow test is not fun.

but right now, that is the gold standard for measuring prognosis and minimal residual disease. If the technology can be perfected on a

blood level so that we can just draw a blood test and measure MRD this way, we'll have a much better way of determining prognosis without putting the patient through a bone marrow test.

When will a blood based MRD test be potentially available for myeloma patients?

Yeah. I think the most mature methods regarding blood samples for MRD is, uh, mass spectrometry, uh, looking at very small amounts of molecular components. Uh, and light chains uh, the sensitivity of this, of this, uh, method. Uh, it's sort of looking at the same thing as electrophoresis and immuno fixation, but it's, it's extremely much more sensitive.

So even in patients who have zero in their molecular component electrophoresis you can still find, uh, small amounts uh, with, uh, this method.

that's a blood sample. It's very easy for the patients. It's, it's a global test. So you sort of the blood sample represents the whole body while the bone marrow sample is just. Just that point.

So there's several things that are better with this method. So what is left is to see if it's equally good. And probably it's, uh, data. So far, as far as I can interpret them, is that in general it seems to be maybe equally good,

data are still maturing on that. But it's also complimentary so that some patients will be positive in bone marrow and negative in blood and some will be the other way around.

So so it's hard to say that we will be able to move beyond bone marrow.

But at least in patients where you see that there are the negativity comes first in bone marrow and

then in blood, then you might think that it will also relapse first in blood, and then you can follow that patient by a blood sample.

Patients who get negative in blood first and then in the bone marrow is maybe, maybe more difficult to follow with only blood samples. But then again, it's not so important to follow them very closely if you're not acting on the results. So as long as you're not treating MRD relapse, you can discuss that it's maybe not necessary to actually perform regular bone marrow to follow this

Can blood based MRD testing be used in non secretory myeloma patients?

Because the blood sample we discuss now is, uh, minute amounts of light chains and molecular components.

If, uh, cancer cells have stopped producing them or produces them to such a small amount that it's not detectable, you can be negative there.

so let's say you have a myeloma cell that doesn't produce anything, then you won't see anything, no matter how many cells you have left in the body. So that's that's the reason

non-secretory is a very easy example of this but it's also about low secretory

when you have quite few myeloma cells left in your body, uh, and they don't secrete that much, there's, there's a limit to the detection level in the blood. But that will also, as everything else, would probably also increase, uh, we will increase the sensitivity of those samples.

Also, I guess as time goes by

There are new technologies that are coming to the field allowing MRD testing to be done in the blood.

They include, for example, detection of circulating free myeloma DNA that could be shedded from the myeloma cells, say, in the bone marrow into the blood, and you can detect it in the blood. Or there could be individual myeloma cells that have been circulating out of the bone marrow, out in the blood. So you could look for individual myeloma cells detected in the in the peripheral blood or free DNA.

You could also look for fragments or proteins in the blood. You could use technologies such as mass spec, and you can look for peptides or fragments of immunoglobulins in the blood. All this blood based technologies are still research, but they are coming fast to the field. And we think that probably the first FDA approvals for these technology, it could happen in say, one or two years or so.

These are estimations. So we will see what the data really delivers