Role of MRD Assessment in Myeloma


Cristina Gasparetto, MD, leads the discussion on whether MRD testing can influence treatment decisions for newly diagnosed multiple myeloma.

Keith Stewart, MD, ChB, MBA: I want to spend a couple of minutes on MRD [minimal residual disease] testing. Cristina, are you doing MRD testing at your center, the Duke Cancer Institute, and if so, what technology are you using?

Cristina Gasparetto, MD: I do. Next-generation sequencing is probably the most used, has the highest sensitivity, is centralized, is approved, etc. But we also have flow cytometry, our pathology colleagues do a phenomenal job with 8-color analysis, with a very reliable 10-5. I use it a lot. I like the sequential, sustained MRD negativity. A lot of the time I use consolidation until I reach the MRD, then sustain it and maybe switch to a maintenance therapy. I always keep the proteasome inhibitor [PI] for the high-risk patient, no matter what. Fortunately, my patients know I’m trying to be very aggressive with the MRD sequential testing. I don’t know much, don’t ask me a lot about mass spec [mass spectrometry], but I was quite impressed by some of the results that were given about whether mass spec can be used together or maybe to replace MRD, so we don’t have to do the frequent bone marrow testing, particularly with the high risk. We tend to do it every 6 months because we don’t want them to go out of the MRD negativity. I’m very interested to see how that will pan out.

Keith Stewart, MD, ChB, MBA: Mass spec is used to detect monoclonal protein in the blood.

Cristina Gasparetto, MD: Yes.

Keith Stewart, MD, ChB, MBA: Before I go on to mass spec, which I do want to hear other opinions on, Nina, you said you would treat with Revlimid [lenalidomide] forever. Do you use MRD? If you’re going to use Revlimid forever, why bother using MRD testing?

Nina Shah, MD: I don’t use MRD testing; it’s not that I never get it, I get it for fun, but I don’t use it to make a decision. The reason for that is because we don’t have data to make that decision. All we know is that people who stop lenalidomide do worse than people who continue lenalidomide. That’s why I tend to give it indefinitely, as long as it’s tolerated.

Keith Stewart, MD, ChB, MBA: I’d love to come to your tumor boards with Jeffrey

Wolf, MD, and Thomas Martin, MD, because they love MRD testing.

Cristina Gasparetto, MD: Oh, I know. That’s why I get all these extra phone calls about it.

Keith Stewart, MD, ChB, MBA: Joseph, are you using MRD testing?

Joseph Mikhael, MD: I think Nina’s correct. We use it, and it informs prognosis, and maybe in some extraneous circumstances, it might influence what you do. But in general, to use it as a decision tool is too preliminary. Sagar already showed us that sometimes it can be misleading as a single test. The sustained testing may guide us with time, but until we do trials that target MRD negativity and randomize thereafter—because there are extremes of myeloma, very low-risk patients who are going to live a long time who don’t get MRD negativity. There are also very high-risk patients who get to MRD negative, but they still need treatment. So I think it’s dangerous to do a lot of changing.

Keith Stewart, MD, ChB, MBA: I agree with Cristina. When I was at the Mayo Clinic—it’s a different world up here in Canada—I used it a lot to de-escalate or escalate therapy. I’m going to go to our deciding vote and turn to Sagar. Sagar, are you using MRD testing? If so, when, how, and why?

Sagar Lonial, MD, FACP: We’re collecting the data. I don’t think we’re using it to influence immediate treatment decisions. The 1 caveat to that is somebody who’s 2 years into lenalidomide maintenance and really struggling to stay on it, such as if they have lots of GI [gastrointestinal] stuff that I can’t make go away or lots of fatigue. If I get an MRD that’s been sustained negative for 2 years, or 1 year depending upon the timeframe, I may feel more comfortable telling them to stop or that it’s OK. But I think using it to make those kinds of decisions in the absence of objective data is jumping the gun on where the technology is taking us.

Keith Stewart, MD, ChB, MBA: What about the MASTER clinical trial? This is a study from Luciano J. Costa, MD, PhD, and the University of Birmingham in Alabama. He has a study where he’s deliberately stopping all treatment if MRD negativity is achieved on 2 different occasions. His results are very impressive. Sagar, what do you think?

Sagar Lonial, MD, FACP: What I worry about is that those 2 independent measures are a month, or 2 months apart. I don’t think they’re sufficiently far enough apart, particularly in the high-risk group, which were about a quarter of the patients enrolled in that trial, to able to answer this question. I suspect we’re going to see with the next update that a lot of the high-risk patients have started to relapse because there we know that stopping early is a mistake.

Keith Stewart, MD, ChB, MBA: Well, there you have it folks. We’ll close up our session on newly diagnosed myeloma. We’ve heard about triplets, increasingly quadruplets, and transplant still has a place. We’re still using Revlimid maintenance for a long duration, some of us are beginning to use MRD, and some people are adding other agents, particularly in the high-risk population. We’ll close out this section now.

Transcript Edited for Clarity

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