Improving Outcomes in Newly Diagnosed Multiple Myeloma - Episode 9

Minimal Residual Disease as a Biomarker in Multiple Myeloma

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What needs to be investigated further before adopting MRD assessments for multiple myeloma into routine clinical practice.

Saad Z. Usmani, MD: One thing that we haven’t touched upon, before we go to the next section, is the utility of MRD [minimal residual disease] testing in our clinical practice. We all recognize it’s an important prognostic tool, and we’ve talked about clinical trials that are looking at this as a therapy-duration-defining kind of a tool. But do you think we’re there yet? I’ve heard a lot of my colleagues are making treatment decisions based on achieving or sustaining MRD already. Where do you guys fall on that? Do you want to see more data? Are we there? Should we be defining treatment duration or changing treatments based on MRD results, Urvi?

Neha Korde, MD: I’m happy to jump in on that.

Saad Z. Usmani, MD: Go ahead, Neha.

Neha Korde, MD: I don’t think we’re yet there. I think we are in a gathering data phase at this point. I think the questions that are being asked, for instance, by the MASTER study, are fascinating. I think this is a roadmap to where we want to go. Are we there yet? The answer, to me, is probably no. When I look at our smaller phase 2 study where we tailored treatment around how many cycles to give, based on MRD response, even though some of that data is maturing, I don’t think it’s quite there yet. We need more sustainable MRD time points.

What I’d like to see, from the field, is the MRD year by year, what the chances are of relapse, and how can we come off of therapy. I also feel like this is going to be important to define, depending on the risk category. I don’t think that, for instance, a standard-risk myeloma patient that is MRD sustainable for years, is the same thing as a high-risk MRD-negative patient who’s managed to do it once and then we make a treatment decision. I feel, at this point, it’s a little too early to make those decisions.

Urvi Shah, MD: Actually, the MASTER trial shows that very specifically, too.

Neha Korde, MD: It does.

Urvi Shah, MD: In the MASTER study, they divided the patients into groups of 0 high-risk cytogenetic abnormalities, 1 cytogenetic abnormality, and 2 cytogenetic abnormalities. The high-risk features that they call are for translocation 4;14, translocation 14;16, deletion 17p, gain of chromosome 1q, and I missed 1, I think.

Urvi Shah, MD: Yeah. Once they stopped maintenance, they looked at patients at the 1 year landmark and who relapsed, or had a biochemical progression. Of those with 2 high-risk cytogenetic abnormalities, 27% of them had a recurrence of disease. Whereas, in the 0 to 1 cytogenetic abnormality, there was almost 0% or 4% patients who did. So I think that’s important to have sustained MRD negativity at 2 time points, and it may not be the same for all patients, depending on risk.

Saad Z. Usmani, MD: This is cool. You’ve heard me talk about all the fun things that Dr Bart Barlogie used to think about and teach. One of those things was before the MRD test: the sustained CR [complete response]. His thing was that sustained CR is most important for high-risk patients. As our tools are getting better, we’re seeing this recurrent theme in some of those concepts. We are going to be relying on sustained MRD negativity. I think it makes more sense, maybe even near 10-6, or maybe higher, for high-risk patients. Lower thresholds may be relevant to standard-risk patients, but I agree. I think sustained MRD is probably going to be the time point, or the first time point, we’re thinking about.

Sham Mailankody, MD: Until the studies come, I think I would use the other factors that all of you guys have mentioned. As for high-risk cytogenetics, how well has the patient responded? How are they tolerating maintenance? I generally tell my patients that I would at least do a minimum of 2 years because there are no studies of maintenance less than 1 to 2 years. Beyond that, if they’re tolerating it well and things are going well, maybe continue treatment but have a discussion of the pros and cons of stopping—particularly if they have sustained MRD negativity, are lower risk, or have had side effects with the ongoing maintenance therapy. That’s a small group of patients, but those patients may do OK with coming off of maintenance at some point and being monitored closely off of maintenance. Dr Neha Korde’s study is a study that addresses that same question for patients with sustained MRD negativity.

Saad Z. Usmani, MD: Yeah. It’s maturing nicely. Stay tuned everyone, that data is coming.

Transcript edited for clarity.