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KRd for High-Risk Smoldering Myeloma

Panelists: John Leonard, MD, New York-Presbyterian/Weill Cornell Center for Lymphoma and Myeloma; C. Ola Landgren, MD, Memorial Sloan Kettering Cancer Center; Alexander Perl, MD, Perelman School of Medicine, University of Pennsylvania; Anas Younes, MD, Memorial Sloan Kettering Cancer Center
Published: Thursday, Dec 07, 2017



Transcript:

John Leonard, MD: Now, time to shift gears over to multiple myeloma and Ola. It’s great to have you here and your perspectives on a number of the different abstracts that are going to be presented. One of the things that we wanted to start with was the concept of smoldering myeloma and high-risk smoldering myeloma. We were talking before the discussion about the fact that some of this is semantics as to where you draw the line, and the parallels between other lymphoid malignancies and the early disease or early stage versus later stage. And the concept of smoldering myeloma seems to be more and more important for people in practice to understand. So, before we get to these abstracts, just a minute or so on what is smoldering myeloma, and what are the key points as one thinks about it?

C. Ola Landgren, MD: Well, I think you really focused on a very important area. I see this a lot in my practice. I get a lot of referrals, and a lot of private practice doctors don’t really know if this is myeloma with the new criteria, because the new myeloma criteria were updated just 2 years ago. So, you don’t have to be sick for it to be called myeloma. There could be biomarkers.

I think the long story short is that smoldering myeloma has certain criteria. You are not supposed to have any of the end-organ damage between renal failure, anemia, bone lesions, and those types of things. And also, there are 3 other biomarkers. There are the light chains being over certain thresholds, high plasma cell infiltration in the marrow, and/or MRI changes in the bone marrow. If you don’t have that, you could now fit with the smoldering category. I think it’s important here to say that at this point, there is still no FDA-approved drug for patients who do fulfill some criteria for smoldering myeloma. If you have more than 10% plasma cells and/or if you have an M-spike greater than 3 g/dL in the absence of these myeloma factors, you have small-grade myeloma. And you should not treat these patients outside of a clinical trial. That’s important. But I think the field is changing. That’s what ASH is really shedding a lot of light on.

John Leonard, MD: Yes, so there are a number of very interesting studies. I think we’re just going to hit a couple of them. But one was the study from Mateos, which, to me, is in some ways very aggressive. On the other hand, it is in some ways smart. And this is like throwing the kitchen sink, almost, to a smoldering myeloma patient and you can say that’s overkill, or you could say maybe you’re going to cure patients with it. So, what’s you take on this study and tell us a little about it.

C. Ola Landgren, MD: So, the Mateos study is a follow-up on 2 other studies that have been done in the past few years. In 2012, the same group from Spain, Mateos, they published, in The New England Journal of Medicine, a randomized study between lenalidomide/dexamethasone versus observation. There were 60 patients in each of the 2 arms. And they found that that was associated with both progression-free and overall survival. So, as a follow-up on that, we led a study, when I was at the NCI, where we added carfilzomib to Revlimid (lenalidomide)/dexamethasone in a single-arm study. And we showed in that study that we could have 100% complete response rate, and there were 95% MRD rates. So, it would make sense to see if could you expand on that. And that’s exactly what this study is about.

They enrolled 90 patients across Spain in a multicenter fashion, and they treated them with the same therapy we used at the NCI. But they also added transplant. At this time, when they present at ASH, this is the first presentation from this study. They only have a few patients who have completed all the therapy. And so far, the numbers look very similar to the NCI study. But I think the key question would be, long-term, could there be a big difference if you add a transplant or not in terms of efficacy? And it is too early. But I think the study is going to be important because it will answer an important question: Should you use your most aggressive treatment out front? We don’t know.

John Leonard, MD: Right. So, do you think, ultimately, we’ll end up answering this question by some sort of big randomized trial of not much therapy or no therapy versus the more aggressive therapy? The myeloma group seemed to have done those sorts of trials much better than we have, I’d say, in lymphoma.

C. Ola Landgren, MD: So, there is actually already a study coming very soon using the same regimen that was done at the NCI with KRd, without the transplant, in a randomized study versus Revlimid/dexamethasone. And that’s going through the European Myeloma Network and also participating sites. We are opening it at Memorial Sloan Kettering Cancer Center as well.

John Leonard, MD: Great.

Transcript Edited for Clarity 
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Transcript:

John Leonard, MD: Now, time to shift gears over to multiple myeloma and Ola. It’s great to have you here and your perspectives on a number of the different abstracts that are going to be presented. One of the things that we wanted to start with was the concept of smoldering myeloma and high-risk smoldering myeloma. We were talking before the discussion about the fact that some of this is semantics as to where you draw the line, and the parallels between other lymphoid malignancies and the early disease or early stage versus later stage. And the concept of smoldering myeloma seems to be more and more important for people in practice to understand. So, before we get to these abstracts, just a minute or so on what is smoldering myeloma, and what are the key points as one thinks about it?

C. Ola Landgren, MD: Well, I think you really focused on a very important area. I see this a lot in my practice. I get a lot of referrals, and a lot of private practice doctors don’t really know if this is myeloma with the new criteria, because the new myeloma criteria were updated just 2 years ago. So, you don’t have to be sick for it to be called myeloma. There could be biomarkers.

I think the long story short is that smoldering myeloma has certain criteria. You are not supposed to have any of the end-organ damage between renal failure, anemia, bone lesions, and those types of things. And also, there are 3 other biomarkers. There are the light chains being over certain thresholds, high plasma cell infiltration in the marrow, and/or MRI changes in the bone marrow. If you don’t have that, you could now fit with the smoldering category. I think it’s important here to say that at this point, there is still no FDA-approved drug for patients who do fulfill some criteria for smoldering myeloma. If you have more than 10% plasma cells and/or if you have an M-spike greater than 3 g/dL in the absence of these myeloma factors, you have small-grade myeloma. And you should not treat these patients outside of a clinical trial. That’s important. But I think the field is changing. That’s what ASH is really shedding a lot of light on.

John Leonard, MD: Yes, so there are a number of very interesting studies. I think we’re just going to hit a couple of them. But one was the study from Mateos, which, to me, is in some ways very aggressive. On the other hand, it is in some ways smart. And this is like throwing the kitchen sink, almost, to a smoldering myeloma patient and you can say that’s overkill, or you could say maybe you’re going to cure patients with it. So, what’s you take on this study and tell us a little about it.

C. Ola Landgren, MD: So, the Mateos study is a follow-up on 2 other studies that have been done in the past few years. In 2012, the same group from Spain, Mateos, they published, in The New England Journal of Medicine, a randomized study between lenalidomide/dexamethasone versus observation. There were 60 patients in each of the 2 arms. And they found that that was associated with both progression-free and overall survival. So, as a follow-up on that, we led a study, when I was at the NCI, where we added carfilzomib to Revlimid (lenalidomide)/dexamethasone in a single-arm study. And we showed in that study that we could have 100% complete response rate, and there were 95% MRD rates. So, it would make sense to see if could you expand on that. And that’s exactly what this study is about.

They enrolled 90 patients across Spain in a multicenter fashion, and they treated them with the same therapy we used at the NCI. But they also added transplant. At this time, when they present at ASH, this is the first presentation from this study. They only have a few patients who have completed all the therapy. And so far, the numbers look very similar to the NCI study. But I think the key question would be, long-term, could there be a big difference if you add a transplant or not in terms of efficacy? And it is too early. But I think the study is going to be important because it will answer an important question: Should you use your most aggressive treatment out front? We don’t know.

John Leonard, MD: Right. So, do you think, ultimately, we’ll end up answering this question by some sort of big randomized trial of not much therapy or no therapy versus the more aggressive therapy? The myeloma group seemed to have done those sorts of trials much better than we have, I’d say, in lymphoma.

C. Ola Landgren, MD: So, there is actually already a study coming very soon using the same regimen that was done at the NCI with KRd, without the transplant, in a randomized study versus Revlimid/dexamethasone. And that’s going through the European Myeloma Network and also participating sites. We are opening it at Memorial Sloan Kettering Cancer Center as well.

John Leonard, MD: Great.

Transcript Edited for Clarity 
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