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Evaluating MRD's Role in Multiple Myeloma

Panelists: A. Keith Stewart, MB, ChB, Mayo Clinic; Sagar Lonial, MD, FACP, Emory University School of Medicine; Thomas Martin, MD, UCSF Helen Diller Family; Edward A. Stadtmauer, MD, University of Pennsylvania; Ajai Chari, MD, Mount Sinai Hospital; Amrita Krishnan, MD, FACP, City of Hope Cancer Center
Published: Saturday, Aug 25, 2018



Transcript: 

A. Keith Stewart, MB, ChB: Sagar, are you using MRD in your practice? And if so, where and what do you do with it?

Sagar Lonial, MD, FACP: We’re collecting the information, partnering it with imaging, but we are not using it for routine decision making.

A. Keith Stewart, MB, ChB: Ed, are you employing it?

Edward A. Stadtmauer, MD: I am not using it routinely, but as of this moment, though, I am very enthusiastic about its use in clinical trials. I don’t think we have the right MRD test yet. What I would love is a blood test that tells us about MRD. You could argue that we’ve had, for the past 30 years, MRD testing. It’s known as a serum protein electrophoresis. And so, I think it’s really important to do these clinical trials. It’s really important to have trials that stratify patients based on MRD-negative and MRD-positive status and then do other things with them. But at this point, it’s not something that I clinically use, similar to what Sagar said. I know that the patients who are MRD-positive have a more difficult outcome than the patients who are MRD-negative. I just don’t know what to do with them.

Amrita Krishnan, MD, FACP: I was going to say I would be a little bit cautious, because I bet you all are using it. Say you have someone who has been on lenalidomide, it’s 5 or 6 years, they keep asking you, “When can I stop?” And then you do it to make yourself feel better and to make them feel better if you say, “OK, maybe you can.”

A. Keith Stewart, MB, ChB: So, in those patients, I usually tell them, “You should be stopping this.” They say, “No, I don’t want to.” Right? Actually, I’ll take the stage here. I actually am using it, maybe rightly or wrongly. I’ve been quite deliberately testing for MRD in patients who had been on lenalidomide for a couple of years, maybe to give myself a reason to stop. But on the other hand, if I find that we’ve done it once and it’s quite low and the next time it’s going up, I use that as an excuse to escalate therapy to something more aggressive, even sometimes to go to second transplant, as I mentioned earlier. What about you folks? Am I out there on a limb? I know you’ve been using it, Tom.

Thomas Martin, MD: No. In San Francisco, we use it a lot, especially in the posttransplant setting. So, we check MRD. We’ve been generally using the adaptive next-generation sequencing platform, which gets to 10-6. And so, the data get back and you’re MRD-negative and the patient wants to know that, and yes, that’s the first question that comes out of their mouth. “Can I stop now that I’m MRD-negative?” And, typically, I’ll tell them, “No, let’s check it again in 6 months or a year, maybe at a year.” And it really depends on their side effects. If they’re having any side effects and they’re MRD-negative, then the patient elects to stop therapy, there’s no doubt about it. So, we don’t intentionally use it for decision making, but it is used in decision making definitely.

A. Keith Stewart, MB, ChB: Ajai, last word to you.

Ajai Chari, MD: We don’t even have adaptive licensed in New York state. We can’t use it. But we do use the Flow.

A. Keith Stewart, MB, ChB: You’re always backward there.

Ajai Chari, MD: I know, right? But I think the issues with MRD—I heard Vincent said this at a meeting once—if we get a hemoglobin of 8 from Tom’s center, that patient is going to have a comparable hemoglobin wherever they go. With MRD testing, you could have one site positive, another site negative, one technique positive, the other one negative. So, I think there’s a lot of technological issues. There’s, as I alluded to, the imaging issues. There’s also the issue of, does that patient have residual paraprotein left? I think outside of clinical trials—even there, its utility really should be in newly diagnosed or maintenance settings—the only place I use it is what Amrita was referring to, which is in low-risk patients. Is there a role for potentially discontinuing, especially when there’s toxicity involved? I think that’s where I would feel a little bit more comfortable, but outside of that, I don’t think we have data.

A. Keith Stewart, MB, ChB: A discussion I was in yesterday, somebody made the point that we may all be starting to use it, but in the community, it’s not even on the radar yet. So, in terms of practice changing in the real world, it’s not penetrated yet. So, what I heard was there are a lot of varying opinions: using it aggressively, not using it at all, using it sparingly or as a research tool. I think that just tells us that for this, we are very much in the discovery phase of learning how to use it.

Transcript Edited for Clarity 

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Transcript: 

A. Keith Stewart, MB, ChB: Sagar, are you using MRD in your practice? And if so, where and what do you do with it?

Sagar Lonial, MD, FACP: We’re collecting the information, partnering it with imaging, but we are not using it for routine decision making.

A. Keith Stewart, MB, ChB: Ed, are you employing it?

Edward A. Stadtmauer, MD: I am not using it routinely, but as of this moment, though, I am very enthusiastic about its use in clinical trials. I don’t think we have the right MRD test yet. What I would love is a blood test that tells us about MRD. You could argue that we’ve had, for the past 30 years, MRD testing. It’s known as a serum protein electrophoresis. And so, I think it’s really important to do these clinical trials. It’s really important to have trials that stratify patients based on MRD-negative and MRD-positive status and then do other things with them. But at this point, it’s not something that I clinically use, similar to what Sagar said. I know that the patients who are MRD-positive have a more difficult outcome than the patients who are MRD-negative. I just don’t know what to do with them.

Amrita Krishnan, MD, FACP: I was going to say I would be a little bit cautious, because I bet you all are using it. Say you have someone who has been on lenalidomide, it’s 5 or 6 years, they keep asking you, “When can I stop?” And then you do it to make yourself feel better and to make them feel better if you say, “OK, maybe you can.”

A. Keith Stewart, MB, ChB: So, in those patients, I usually tell them, “You should be stopping this.” They say, “No, I don’t want to.” Right? Actually, I’ll take the stage here. I actually am using it, maybe rightly or wrongly. I’ve been quite deliberately testing for MRD in patients who had been on lenalidomide for a couple of years, maybe to give myself a reason to stop. But on the other hand, if I find that we’ve done it once and it’s quite low and the next time it’s going up, I use that as an excuse to escalate therapy to something more aggressive, even sometimes to go to second transplant, as I mentioned earlier. What about you folks? Am I out there on a limb? I know you’ve been using it, Tom.

Thomas Martin, MD: No. In San Francisco, we use it a lot, especially in the posttransplant setting. So, we check MRD. We’ve been generally using the adaptive next-generation sequencing platform, which gets to 10-6. And so, the data get back and you’re MRD-negative and the patient wants to know that, and yes, that’s the first question that comes out of their mouth. “Can I stop now that I’m MRD-negative?” And, typically, I’ll tell them, “No, let’s check it again in 6 months or a year, maybe at a year.” And it really depends on their side effects. If they’re having any side effects and they’re MRD-negative, then the patient elects to stop therapy, there’s no doubt about it. So, we don’t intentionally use it for decision making, but it is used in decision making definitely.

A. Keith Stewart, MB, ChB: Ajai, last word to you.

Ajai Chari, MD: We don’t even have adaptive licensed in New York state. We can’t use it. But we do use the Flow.

A. Keith Stewart, MB, ChB: You’re always backward there.

Ajai Chari, MD: I know, right? But I think the issues with MRD—I heard Vincent said this at a meeting once—if we get a hemoglobin of 8 from Tom’s center, that patient is going to have a comparable hemoglobin wherever they go. With MRD testing, you could have one site positive, another site negative, one technique positive, the other one negative. So, I think there’s a lot of technological issues. There’s, as I alluded to, the imaging issues. There’s also the issue of, does that patient have residual paraprotein left? I think outside of clinical trials—even there, its utility really should be in newly diagnosed or maintenance settings—the only place I use it is what Amrita was referring to, which is in low-risk patients. Is there a role for potentially discontinuing, especially when there’s toxicity involved? I think that’s where I would feel a little bit more comfortable, but outside of that, I don’t think we have data.

A. Keith Stewart, MB, ChB: A discussion I was in yesterday, somebody made the point that we may all be starting to use it, but in the community, it’s not even on the radar yet. So, in terms of practice changing in the real world, it’s not penetrated yet. So, what I heard was there are a lot of varying opinions: using it aggressively, not using it at all, using it sparingly or as a research tool. I think that just tells us that for this, we are very much in the discovery phase of learning how to use it.

Transcript Edited for Clarity 
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