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MRD Monitoring in Multiple Myeloma

Panelists:Keith Stewart, MD, CHB, Mayo Clinic;William I. Bensinger, MD, Swedish Cancer Institute;Rafael Fonseca, MD, Mayo Clinic;C. Ola Landgren, MD, PhD, Memorial Sloan Kettering Cancer Center;Jatin P. Shah, MD, MD Anderson Cancer Center
Published Online: Wednesday, Sep 07, 2016



Transcript:

Keith Stewart, MD, CHB:
I’m thinking that now we’re going to be using carfilzomib, pomalidomide, daratumumab, and dexamethasone at relapse. That sounds like where we’re going here. We’re going to have incredibly high response rates, probably I would guess over half the people entering complete remission even in relapse. Tell us about MRD monitoring. Do you stop treatment based on that? If you get MRD negativity after, let’s say, a year of treatment, do you keep going or do you just stop, Ola?

C. Ola Landgren, MD, PhD: So, in our practice we check for MRD status in every patient who reaches CR. We have that as a model across the whole program, and we do not…

Keith Stewart, MD, CHB: If I’m a community oncologist, where do I send a sample, how do I get this done?

C. Ola Landgren, MD, PhD: For the flow cytometry, you certainly need to set up your program so you can do it right. And I think the Spanish model, the EuroFlow, is the most well published, but there are other alternative models out there also. That includes panels with a series of antibodies…

Keith Stewart, MD, CHB: Are they available commercially anywhere or is this something you have to get done in academics?

C. Ola Landgren, MD, PhD: It is published, and the labs that run flow cytometry panels can implement that, and everything is available in the literature. So, I think it’s more a matter of having the lab calibrating the way of doing the flow. For the molecular testing for right now, the provider out in California, Adaptimmune, they offer the ClonoSIGHT testing.

Keith Stewart, MD, CHB: And that’s a Sandoz test?

C. Ola Landgren, MD, PhD: That’s a Sandoz test for sequencing.

Keith Stewart, MD, CHB: When you get it and it comes back negative, are you using that as a decision point to stop or are you using…?

C. Ola Landgren, MD, PhD: At this point, we do not. Usually that’s a decision point to stop. But, as I told you before, for newly diagnosed patients, if you are MRD-negative to the deepest degree, we have this conversation that we are unsure whether the up-front delivery of melphalan is going to add PFS.

Keith Stewart, MD, CHB: I guess I’m troubled by this notion that you just treat forever. What does that mean? Is it 5 years, 10 years? At some point, you have to say enough is enough. Or is this CML where you treat for life?

C. Ola Landgren, MD, PhD: I can tell you what we’re doing in our research program at our institution. It’s interesting to hear what other people are doing here at the table. So, at our institution we do 5 years of follow-up and we do MRD testing longitudinally. And if you have maintained MRD for 5 years, which no one so far has done on this program, the intent is to bring up the question, do you want to go off maintenance or not? And we will continue monitoring to just see what the data tell us. We don’t know right now.

Keith Stewart, MD, CHB: Rafael, are you using MRD monitoring?

Rafael Fonseca, MD: I am. And, I think there’s a human aspect of this which is so important because I have tested patients who have been on long-term maintenance approaches, or chronic therapy with lenalidomide, where I propose that we do MRD to make a decision. And the test is the easy part, what’s hard is the discussion. So, the patient is going to ask me, “Can you assure me that this is good enough?” And I say, “I don’t know, it’s very appealing.” I think how I would use it is if the patient is burdened by the symptoms for maintenance, maybe I would push more for that and say, “Let’s consider stopping”—what we did before without MRD. But if the patient is tolerating it well, then it’s sometimes a hard sell because they say, “I don’t know, it’s working well for me, why do I want to change?”

Keith Stewart, MD, CHB: I must admit, people on lenalidomide, they’ve got some chronic fatigue, a little bit of diarrhea, come back MRD negative after 2 or 3 years of maintenance. I have used that as a criteria for discontinuing it. Anybody else?

Jatin P. Shah, MD: Does that change based on this meta-analysis saying that you have an overall survival image?

Keith Stewart, MD, CHB: No, no, I don’t think so. I think it’s, to me getting into MRD negativity is the point. And once you’re there…

C. Ola Landgren, MD, PhD: So, have you followed MRD over time? Do you see…

Keith Stewart, MD, CHB: No, because we’ve only started using it in the last 6 months so we’re just beginning to…

C. Ola Landgren, MD, PhD: I think that’s the next question, obviously. You need to…

Keith Stewart, MD, CHB: Well, yes. The plan would be to bring them back and repeat it in 6 months.

C. Ola Landgren, MD, PhD: Right.

Keith Stewart, MD, CHB: We initiate therapy if we saw…

Rafael Fonseca, MD: Well, there’s a lot of applications. I’ll give another example. A patient with high-risk disease where we did a bone marrow 1 year out, MRD-negative. I was quick to get on the phone and tell that person, “Guess what, we’re in the right; we’re not changing anything,” but that’s quite useful for a person that knows that they’ve got high-risk disease. And, now, minus 17p, the patient’s MRD-negative by NGS.

C. Ola Landgren, MD, PhD: If I recall correctly, the CML data, for chronic myeloid leukemia, show that if you reach MRD negativity, you maintain it for about 2 years. If you go off therapy, half of the patients have no relapse and half do.

Keith Stewart, MD, CHB: The other half do, yes.

C. Ola Landgren, MD, PhD: But, we can retreat them down to MRD negativity again. So, I think that’s the data we need to generate for myeloma.

Keith Stewart, MD, CHB: Any other thoughts before we move on to new drugs?

William I. Bensinger, MD: I agree.

Transcript Edited for Clarity

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Transcript:

Keith Stewart, MD, CHB:
I’m thinking that now we’re going to be using carfilzomib, pomalidomide, daratumumab, and dexamethasone at relapse. That sounds like where we’re going here. We’re going to have incredibly high response rates, probably I would guess over half the people entering complete remission even in relapse. Tell us about MRD monitoring. Do you stop treatment based on that? If you get MRD negativity after, let’s say, a year of treatment, do you keep going or do you just stop, Ola?

C. Ola Landgren, MD, PhD: So, in our practice we check for MRD status in every patient who reaches CR. We have that as a model across the whole program, and we do not…

Keith Stewart, MD, CHB: If I’m a community oncologist, where do I send a sample, how do I get this done?

C. Ola Landgren, MD, PhD: For the flow cytometry, you certainly need to set up your program so you can do it right. And I think the Spanish model, the EuroFlow, is the most well published, but there are other alternative models out there also. That includes panels with a series of antibodies…

Keith Stewart, MD, CHB: Are they available commercially anywhere or is this something you have to get done in academics?

C. Ola Landgren, MD, PhD: It is published, and the labs that run flow cytometry panels can implement that, and everything is available in the literature. So, I think it’s more a matter of having the lab calibrating the way of doing the flow. For the molecular testing for right now, the provider out in California, Adaptimmune, they offer the ClonoSIGHT testing.

Keith Stewart, MD, CHB: And that’s a Sandoz test?

C. Ola Landgren, MD, PhD: That’s a Sandoz test for sequencing.

Keith Stewart, MD, CHB: When you get it and it comes back negative, are you using that as a decision point to stop or are you using…?

C. Ola Landgren, MD, PhD: At this point, we do not. Usually that’s a decision point to stop. But, as I told you before, for newly diagnosed patients, if you are MRD-negative to the deepest degree, we have this conversation that we are unsure whether the up-front delivery of melphalan is going to add PFS.

Keith Stewart, MD, CHB: I guess I’m troubled by this notion that you just treat forever. What does that mean? Is it 5 years, 10 years? At some point, you have to say enough is enough. Or is this CML where you treat for life?

C. Ola Landgren, MD, PhD: I can tell you what we’re doing in our research program at our institution. It’s interesting to hear what other people are doing here at the table. So, at our institution we do 5 years of follow-up and we do MRD testing longitudinally. And if you have maintained MRD for 5 years, which no one so far has done on this program, the intent is to bring up the question, do you want to go off maintenance or not? And we will continue monitoring to just see what the data tell us. We don’t know right now.

Keith Stewart, MD, CHB: Rafael, are you using MRD monitoring?

Rafael Fonseca, MD: I am. And, I think there’s a human aspect of this which is so important because I have tested patients who have been on long-term maintenance approaches, or chronic therapy with lenalidomide, where I propose that we do MRD to make a decision. And the test is the easy part, what’s hard is the discussion. So, the patient is going to ask me, “Can you assure me that this is good enough?” And I say, “I don’t know, it’s very appealing.” I think how I would use it is if the patient is burdened by the symptoms for maintenance, maybe I would push more for that and say, “Let’s consider stopping”—what we did before without MRD. But if the patient is tolerating it well, then it’s sometimes a hard sell because they say, “I don’t know, it’s working well for me, why do I want to change?”

Keith Stewart, MD, CHB: I must admit, people on lenalidomide, they’ve got some chronic fatigue, a little bit of diarrhea, come back MRD negative after 2 or 3 years of maintenance. I have used that as a criteria for discontinuing it. Anybody else?

Jatin P. Shah, MD: Does that change based on this meta-analysis saying that you have an overall survival image?

Keith Stewart, MD, CHB: No, no, I don’t think so. I think it’s, to me getting into MRD negativity is the point. And once you’re there…

C. Ola Landgren, MD, PhD: So, have you followed MRD over time? Do you see…

Keith Stewart, MD, CHB: No, because we’ve only started using it in the last 6 months so we’re just beginning to…

C. Ola Landgren, MD, PhD: I think that’s the next question, obviously. You need to…

Keith Stewart, MD, CHB: Well, yes. The plan would be to bring them back and repeat it in 6 months.

C. Ola Landgren, MD, PhD: Right.

Keith Stewart, MD, CHB: We initiate therapy if we saw…

Rafael Fonseca, MD: Well, there’s a lot of applications. I’ll give another example. A patient with high-risk disease where we did a bone marrow 1 year out, MRD-negative. I was quick to get on the phone and tell that person, “Guess what, we’re in the right; we’re not changing anything,” but that’s quite useful for a person that knows that they’ve got high-risk disease. And, now, minus 17p, the patient’s MRD-negative by NGS.

C. Ola Landgren, MD, PhD: If I recall correctly, the CML data, for chronic myeloid leukemia, show that if you reach MRD negativity, you maintain it for about 2 years. If you go off therapy, half of the patients have no relapse and half do.

Keith Stewart, MD, CHB: The other half do, yes.

C. Ola Landgren, MD, PhD: But, we can retreat them down to MRD negativity again. So, I think that’s the data we need to generate for myeloma.

Keith Stewart, MD, CHB: Any other thoughts before we move on to new drugs?

William I. Bensinger, MD: I agree.

Transcript Edited for Clarity
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