What is the role of imaging in MRD testing?

What is the role of imaging in MRD Testing.

In the response criteria, you have the first level of MRD negativity. That's the bone marrow test. And the next level is when you're also negative in the pet. And today the guidelines are a glucose pet. So it's only showing metabolic activations lesions. And we know that the prognosis of patients that have remaining active metabolic lesions that are interpreted as myeloma after their first line treatment, it's a very, very bad prognostic sign.

So the pet is complimentary in another way you can have a bone marrow sample where there's no myeloma cells there, but there are foci, other places and the PET scan them and then patients show that and that's also part of a worse prognosis. So I think maybe the more a very interesting thing is to see how the pet and the blood sample mass-spec will compare, because they're both sort of testing the whole body while the Bone and NGF and NGS are both testing just myeloma cells in the particular bone marrow sample.

So they sort of two two unifocals and two global tests and probably and and they will be complementary of all of this but the pet and the blood sample are sort of more convenient for the patient, of course, than regular bone marrows.

Also, imaging is included. there is another criteria beyond just MRD negativity. So there is something called MRD negativity with imaging included. That means that the patients could be worked up with the bone marrow biopsy found to be negative with an assay 10 to -5 or better. And if pet CT is done and there is no abnormal uptake, then the patient would be negative with both.

There are some individuals that are negative in the bone marrow, but they could still have some areas positive with pet CT. If that happens, the patient could still fulfill the definition under criteria for MRD negativity, but there should be a comment in the note that the patient is MRD negative 10 to minus five. But the pet CT identifies residual disease if the patient is monitored, is on therapy.

If pet CT is repeated and this area goes away, there is no abnormal uptake. The note should then say the patient is MRD negative and now the pet CT is negative. It seems that clinically patients who are MRD negative with both the bone marrow and the pet CT is negative that the prognosis is even better compared to an individual who is truly MRD negative in the bone marrow but has some uptake in the in the in the pet.

So being negative with both is the best.

How are PET CT scans used to help determine MRD negativity?

You have heard a bit about MRD measurement. It's minimal residual disease. You have heard it's very important that this is as low as possible, that the response to treatment should be as good as possible. The problem is when we are negative with our free light chains, negative with the immunofixation negative in the urine, we still can have some disease in the in the bone marrow.

And then we do bone marrow biopsy here, which is the easiest way to get it. But the problem is that in a in a French trial, it was mentioned several times now they found that you can be pet negative pet or MRI, either one negative, an MRD positive so you can stick a needle here. PET is overall negative and you think, okay, great.

Then you stick a needle in here and you’re still MRD positive. Or you can be MRD negative. You stick a needle in here, but you have something growing here. So it's very important to have the whole picture in the whole picture, meaning as much of the body to image as you can, plus doing this very sensitive technique with the bone marrow.

That's also a question oftentimes coming from patients, since we have this very sensitive and great imaging techniques to really still need bone marrow. The bad news is, yes, at the moment we still need it because we have to see how many of the patients, the sensitivity of the bone marrow biopsy is still much higher than our imaging techniques.

But we are getting there. And I you promise you, then we can get rid of bone marrow. So don't get me wrong. So this is kind of demonstrating that you can see again, this dark spot, which is a myeloma lesion. If you put in a needle here, it might be be positive. If you put it in this lighter gray spot, it might be negative.

So as again, I think it's very important to do imaging plus MRD assessment plus our serum and urine analysis. And this is showing if both is negative, MRD is negative and imaging is negative, then the prognosis is very good. And that's what we are going for.