Who should get MRD testing?

Who is the right patient to get MRD testing?

A common question in the clinical setting is who is the right patient for MRD testing.

Going back to guidelines, the NCCN guideline would endorse the testing with MRD assays in a patient who is newly diagnosed and who has completed combination therapy and is about to collect stem cells. That could be the first time when MRD testing could be done. A patient who is undergoing bone marrow transplant after transplant, that could also be done.

This could happen in the same patient before and after transplant. And if the patient collects the stem cells and doesn't do the transplant, do a delayed transplant that is increasingly more common over time. If the patient goes back to combination therapy after additional cycles being given. Again, testing could be done. So a scenario could be four cycles of therapy MRD testing with collection of stem cells, another four cycles of therapy MRD testing and delayed transplant and go to maintenance.

If a patient goes to maintenance to check it on an annual basis would also be endorsed by the NCCN guideline. The guidelines say thatpatients that are in a complete response, if they have no detectable cells in the MRD assay in the bone marrow, that would formally be MRD Negative. But what is now being found in many studies is that patients can be MRD negative in the bone marrow, and there could still be some little protein left. 

So what does that mean? Well, probably that the therapies are so fast to get rid of the myeloma cells, while the proteins that these myeloma cells made could be lingering longer in the body and they have not yet been cleared out.

So they give some false signals. So we see more and more, for example, after CAR-T cell therapy or after the four drug combination therapies in the newly diagnosed setting, that the patient could be treated just for a short period of time.

CAR-T cells, you could give CAR-T cells and do a biopsy after one month. The patient could be MRD negative, but the m spike may not have changed at all compared to even before CAR-T cells and it could take many months for that m spike to go away. My Prediction is that the guidelines probably will have to be updated and MRD in the bone marrow most likely will become an independent measuring point that is separated from the protein.

But the field has not yet agreed to that. But that's the direction the field has to be moving.

Who should consider MRD testing? And when should it be done? 

Is there a residual disease in the bone marrow? So at that time, we will obtain a bone marrow sample and we will send it for analysis.

The question of when should MRD be testing? When should MRD testing be performed? Is complex. I think the short answer is that it's not quite ready for prime time in routine practice

for a for many, many reasons. The one of the biggest reasons is that it's not standardized. If you get MRD testing in Heidelberg, it's not going to be the same as in Chicago.

So it cannot be compared. It is not ready for Prime time in routine practice. It is now being done routinely in clinical trials. So in general, I would say we're not quite there. If you're in a clinical trial, which I strongly encourage all patients to be in clinical trials, you probably will have high, high level, MRD testing. So it's still. Studies are still under way.

MRD, when should MRD testing be done is a great question. It depends on the technology that you're using. There's two major forms of technology. One is called flow cytometry, which is can measure cells down to. We can find one abnormal cell or one bad guy in 100,000 normal cells. That's pretty that's amazingly good. When you use another technology called Next next generation sequencing, which is a genetic test, we can identify one bad cell in a million cellswhat we've learned is that the MRD status changes in many patients over time. So if we if we are to use MRD testing, we're going to need to check it again and again. And at least for now, that's going to require repeated bone marrow aspirations.