ASH 2020 Updates: Improving Outcomes in TIE-NDMM - Episode 3

Multiple Myeloma: Incorporating MRD Assessment into Clinical Practice

Insight regarding the assessment of minimal residual disease in patients with multiple myeloma and using testing results to aid in treatment selection.

Rafael Fonseca, MD: MRD [minimal residual disease] is here to stay in the management of multiple myeloma. We have seen multiple studies that show that MRD is critically important as a prognostic factor. We see that in the transplant-eligible population, clearly. We do routine testing for MRD at the time after transplant. This is called the “day 100 visit.” We are also doing this to any patients who have sustained complete responses.

Various clinical trial literature show that MRD can also be used to measure and compare efficacy ofvarious treatments. We see that even in the transplant-ineligible population, a significant fraction of patients are able to obtain MRD negativity. We’ve seen that demonstrated by the MAIA clinical trial. We see that in the ALCYONE study. We see a couple of things.

First, we see that MRD clearly indicates patients who have durable control of their disease. Also, we see that sustained MRD negativity correlates with sustained responses. Some of the patients treated with this type of regimen who get into that MRD-negative status—assuming they tolerate it and complete the treatment—should have, in my mind, particularly those around age 80, a near-normal life expectancy.

One of the next frontiers in the use of MRD is how to react to that knowledge as we think about next steps in therapeutics. There is a growing body of evidence that suggests that no matter what, you need to get to MRD negativity.

Historically, we did that with induction and with transplant. However, there were 2 abstracts presented at ASH [American Society of Hematology Annual Meeting] that showed that continued treatment seems to benefit patients. And we know from the French data that if you achieve MRD negativity, whether that’s at the beginning of maintenance or a year later, it doesn’t matter as long as you get there.

In my mind, the next frontier is if a person who completes a transplant is still MRD positive, should that person just go into simple maintenance or should additional treatment be given? The jury is out on this. I provide additional treatment in the hopes of further reducing the clone. I do so with particular emphasis in those who are younger and have high-risk markers.

At this moment, we have enough information to support that the use of MRD as a prognostic factor should be incontrovertible. There’s no other prognostic factor that has been as powerful as MRD for multiple myeloma. I worked on the first phase of genetic factors in regard to myeloma prognosis. They don’t come close to the value of what you have for MRD. We fortunately have an FDA-approved test for this. In our case, this is routinely used in the clinic.

The next step is to determine how comfortable people are in making clinical decisions based on MRD. We’ve incorporated a number of biomarkers over the years that better inform practice. People often get worried and think, “How am I going to introduce this issue based on MRD?” I say, “The same way you have made decisions based on protein electrophoresis, immunoglobulins, and the free light chain.”

It would be rare, I imagine, that a single determination of MRD would be completely binomial and would tell you to continue or stop therapy. However, it certainly informs your clinical practice, and that’s how I’ll use it.

Transcript edited for clarity.