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Newly Diagnosed Transplant-Eligible Myeloma: The Role of MRD

Panelists: Sagar Lonial, MD, FACP, Winship Cancer Institute of Emory University; Amrita Y. Krishnan, MD, City of Hope Comprehensive Cancer Center; Thomas G. Martin, MD, UCSF Helen Diller Family Comprehensive Cancer Center; Krina K. Patel, MD, MSc, University of Texas MD Anderson Cancer Center; Saad Z. Usmani, MD, FACP, Levine Cancer Institute
Published: Thursday, Jul 11, 2019



Transcript: 

Sagar Lonial, MD, FACP: I think the other question is something we’ve, in the past, spent a lot of time on. This time, let’s try to fit it in here. At least in a newly diagnosed setting, how are you using MRD [minimal residual disease] to drive decisions early on? I’m not talking about at 1 year. I’m talking early on in the induction setting or perhaps around the time of transplant.

Krina K. Patel, MD, MSc: So I actually have a lot of savvy patients who come to me and say, “I’ve heard I don’t need a transplant anymore, based on the IFM [Intergroup Francophone du Myeloma] data.” And so they want MRD done, and I actually do it for some of my patients. And I think after the FORTE trial, I’ll probably have a little bit more data to share with them. But I find my patient really just does not want a transplant. And I’m a transplanter, right? That’s what I was born as. If I can’t convince them, we’ll do MRD after 4 to 6 cycles if they’ve had a CR [complete response], it looks like they’re at a CR. And if they’re negative, we use it. This is not validated or anything. But then we’ll save their cells if we can and then just go on with transplant at relapse. But that’s not very many patients. Most patients agree to do it.

Now, I think with the FORTE data, if I do have ISS [International Staging System] stage I patients who don’t want transplant, and since we do KRd [carfilzomib, lenalidomide, dexamethasone], I think it would be OK potentially. Yes, there’s still better MRD when they did the transplant, but they didn’t have the early relapse as the high-risk patients did. So if we’re looking at PFS [progression-free survival], and that’s what my patients are looking at, then I can use those data to say, OK, maybe those are the patients. But high risk, I would still really try to do transplant.

Sagar Lonial, MD, FACP: You all? I know Tom is a big proponent of MRD at every cycle.

Thomas G. Martin, MD: Well, we do a lot of MRD.

Saad Z. Usmani, MD, FACP: You just leave the needle in there?

Sagar Lonial, MD, FACP: Right.

Thomas G. Martin, MD: The early assessment time point it’s really difficult because there are not a lot of data on what to do at the early assessment. And assessments are typically done post transplant or even 18 months after transplant, so it’s post hoc. Joaquin Martinez-Lopez has an abstract at the American Society of Clinical Oncology Annual Meeting based on real-world data from UCSF [the University of California, San Francisco], and he’s presenting it. And really the value of doing MRD in my mind is this sequential monitoring of MRD, and it’s when sequentially you see continued MRD negativity. Those are the patients who actually do quite well. I will say that we did not intend to do any treatment decisions based on MRD, and so we didn’t make any early treatment decisions based on MRD, but we have made later transplant decisions based on MRD. If somebody is having adverse events and they’re on maintenance, and they’re MRD-negative for 2, the patients want off. And we allow that to happen.

Sagar Lonial, MD, FACP: I will say that we’ve pooled our data on RVd [lenalidomide-bortezomib-dexamethasone] induction, transplant, and maintenance, continuous lenalidomide maintenance in about 1000 patients. And the median PFS in that group is close to 76 months, between 70 and 76 months. That’s pretty good, and so I would suspect the reason we’re not seeing a difference in FORTE is because the follow-up is only 2 years. And so for the standard-risk group, it’s going to take much longer for those curves to separate. But if you’ll remember back when data was presented years ago on CR, transplant versus no transplant, the response rate was identical. CR rate was the same, but the transplant group had a better PFS. I think, to me, MRD is a nice CR that does have prognostic implications, but I’m still a little hesitant to use it to make a decision early.

Saad Z. Usmani, MD, FACP: Same here. The only situation in which it would make sense is the high-risk patients. I don’t think the high-risk patients, I mean, you raised a very good point about the threshold, 10-5 versus 10-6. What’s the real MRD-negativity threshold? I think 10-6 is even more important for the high-risk patients, 10-5 doesn’t mean anything for those patients. And if you have an MRD-negative patient who turns positive, it may not be as a big deal for the standard-risk patients, but it would make us think differently for the high-risk patients and probably change what we’re doing with them.

Transcript Edited for Clarity

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Transcript: 

Sagar Lonial, MD, FACP: I think the other question is something we’ve, in the past, spent a lot of time on. This time, let’s try to fit it in here. At least in a newly diagnosed setting, how are you using MRD [minimal residual disease] to drive decisions early on? I’m not talking about at 1 year. I’m talking early on in the induction setting or perhaps around the time of transplant.

Krina K. Patel, MD, MSc: So I actually have a lot of savvy patients who come to me and say, “I’ve heard I don’t need a transplant anymore, based on the IFM [Intergroup Francophone du Myeloma] data.” And so they want MRD done, and I actually do it for some of my patients. And I think after the FORTE trial, I’ll probably have a little bit more data to share with them. But I find my patient really just does not want a transplant. And I’m a transplanter, right? That’s what I was born as. If I can’t convince them, we’ll do MRD after 4 to 6 cycles if they’ve had a CR [complete response], it looks like they’re at a CR. And if they’re negative, we use it. This is not validated or anything. But then we’ll save their cells if we can and then just go on with transplant at relapse. But that’s not very many patients. Most patients agree to do it.

Now, I think with the FORTE data, if I do have ISS [International Staging System] stage I patients who don’t want transplant, and since we do KRd [carfilzomib, lenalidomide, dexamethasone], I think it would be OK potentially. Yes, there’s still better MRD when they did the transplant, but they didn’t have the early relapse as the high-risk patients did. So if we’re looking at PFS [progression-free survival], and that’s what my patients are looking at, then I can use those data to say, OK, maybe those are the patients. But high risk, I would still really try to do transplant.

Sagar Lonial, MD, FACP: You all? I know Tom is a big proponent of MRD at every cycle.

Thomas G. Martin, MD: Well, we do a lot of MRD.

Saad Z. Usmani, MD, FACP: You just leave the needle in there?

Sagar Lonial, MD, FACP: Right.

Thomas G. Martin, MD: The early assessment time point it’s really difficult because there are not a lot of data on what to do at the early assessment. And assessments are typically done post transplant or even 18 months after transplant, so it’s post hoc. Joaquin Martinez-Lopez has an abstract at the American Society of Clinical Oncology Annual Meeting based on real-world data from UCSF [the University of California, San Francisco], and he’s presenting it. And really the value of doing MRD in my mind is this sequential monitoring of MRD, and it’s when sequentially you see continued MRD negativity. Those are the patients who actually do quite well. I will say that we did not intend to do any treatment decisions based on MRD, and so we didn’t make any early treatment decisions based on MRD, but we have made later transplant decisions based on MRD. If somebody is having adverse events and they’re on maintenance, and they’re MRD-negative for 2, the patients want off. And we allow that to happen.

Sagar Lonial, MD, FACP: I will say that we’ve pooled our data on RVd [lenalidomide-bortezomib-dexamethasone] induction, transplant, and maintenance, continuous lenalidomide maintenance in about 1000 patients. And the median PFS in that group is close to 76 months, between 70 and 76 months. That’s pretty good, and so I would suspect the reason we’re not seeing a difference in FORTE is because the follow-up is only 2 years. And so for the standard-risk group, it’s going to take much longer for those curves to separate. But if you’ll remember back when data was presented years ago on CR, transplant versus no transplant, the response rate was identical. CR rate was the same, but the transplant group had a better PFS. I think, to me, MRD is a nice CR that does have prognostic implications, but I’m still a little hesitant to use it to make a decision early.

Saad Z. Usmani, MD, FACP: Same here. The only situation in which it would make sense is the high-risk patients. I don’t think the high-risk patients, I mean, you raised a very good point about the threshold, 10-5 versus 10-6. What’s the real MRD-negativity threshold? I think 10-6 is even more important for the high-risk patients, 10-5 doesn’t mean anything for those patients. And if you have an MRD-negative patient who turns positive, it may not be as a big deal for the standard-risk patients, but it would make us think differently for the high-risk patients and probably change what we’re doing with them.

Transcript Edited for Clarity
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