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The Role of Transplant in Myeloma

Panelists: A. Keith Stewart, MB, ChB, Mayo Clinic; Cristina Gasparetto, MD, Duke University Medical Center; Parameswaran Hari, MD, MRCP, MS, Medical College of Wisconsin; Robert Orlowski, MD, PhD, MD Anderson Cancer Center; Noopur Suresh Raje, MD, Massachusetts General Hospital
Published: Friday, Feb 09, 2018



Transcript: 

A. Keith Stewart, MB, ChB: So, let me just see if I can summarize where we’re at here. Smoldering myeloma still in the trial domain but quite interesting, deep responses, see how far we can take that but wait for the trial results. Is everyone in agreement? Up-front therapy both in the elderly and the younger patient, most of us are agreeing with a triplet approach of a proteasome inhibitor and an IMiD.

We’re on the cusp of adding a fourth drug for young patients, maybe not so much for the elderly patient. And it sounds like all of us are using maintenance with an IMiD and layering on top of that a proteasome inhibitor for the higher-risk patient. Is that a fair summary? A little bit of controversy about transplant. We have a couple minutes left on this. Let’s just talk about that. So, if your patient enters, as Bob suggested, a MRD-negative state, you still transplant them, Hari?

Parameswaran Hari, MD, MRCP, MS: I do for 2 reasons, because the sensitivity level of the MRD tests keep changing. We have people who are MRD-negative at 10-4, or negative at 10-4 can be positive at 10-6. And there are data being presented again that that makes a difference. So, MRD testing is still not perfect. Second, we don’t have sufficient follow-up. People who are MRD-negative, even at the next-generation sequencing 10-6 level, do relapse. MRD does not equate with cure at this point. So, I think for a young person to be denied the most effective platform that has got us here for a long time would be difficult for me to forego that. And second thing, people don’t get younger and better with time. So, if you’re going to do a transplant ever, you better do it earlier.

A. Keith Stewart, MB, ChB: Spoken by a true transplanter. Noopur?

Noopur Suresh Raje, MD: I have plenty of people in my practice who I will not transplant. There are folks where I would suggest—where I’m worried about how they’re going to relapse, with renal disease, for example—transplant may be off the table for those. Those are the ones I am going to encourage to get transplanted, including the high-risk ones. But there are certain standard-risk ones, as long as I’ve collected those cells, I’m quite comfortable watching. I do worry about the older ones I’m watching, 65 to 66, because, as you pointed out, Hari, they’re not getting any younger. And I’d rather get them transplanted and move on.

A. Keith Stewart, MB, ChB: Christina?

Cristina Gasparetto, MD: I think a little bit like Hari. I think it’s still very important. The MRD is our goal, and the number of patients achieving a deeper response is higher with transplant. So, outside of a clinical trial, where we’re not testing, we know with transplant that we achieve a deeper response, so I go there aggressively.

A. Keith Stewart, MB, ChB: Bob, you sticking with your original hypothesis?

Robert Orlowski, MD, PhD: I am. Now, Hari does bring up a good point. When I mentioned MRD, I meant 10-6. It may be interesting to save a sample of the bone marrow and peripheral blood on patients for future testing, like next-generation sequencing. And we’re not denying the patient a transplant. We’re certainly just giving them an option of transplant now versus transplant later. And we know from a number of studies that second-line transplant is just as effective, especially in a younger patient. I agree that if you’ve got somebody who’s pushing 70, you probably don’t want to wait. But the other benefits are they have a better quality of life without transplant and they have a lower risk of second primary malignancies in many studies. So, those are not things to be ignored.

Parameswaran Hari, MD, MRCP, MS: Yes, I completely agree. For the community, the sad part is that only about 35% of patients who are below the age of 70 in the United States actually get to a transplant center. And I think it’s important that collection and holding at the very minimum is something that we should do in all our young patients.

Transcript Edited for Clarity 

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Transcript: 

A. Keith Stewart, MB, ChB: So, let me just see if I can summarize where we’re at here. Smoldering myeloma still in the trial domain but quite interesting, deep responses, see how far we can take that but wait for the trial results. Is everyone in agreement? Up-front therapy both in the elderly and the younger patient, most of us are agreeing with a triplet approach of a proteasome inhibitor and an IMiD.

We’re on the cusp of adding a fourth drug for young patients, maybe not so much for the elderly patient. And it sounds like all of us are using maintenance with an IMiD and layering on top of that a proteasome inhibitor for the higher-risk patient. Is that a fair summary? A little bit of controversy about transplant. We have a couple minutes left on this. Let’s just talk about that. So, if your patient enters, as Bob suggested, a MRD-negative state, you still transplant them, Hari?

Parameswaran Hari, MD, MRCP, MS: I do for 2 reasons, because the sensitivity level of the MRD tests keep changing. We have people who are MRD-negative at 10-4, or negative at 10-4 can be positive at 10-6. And there are data being presented again that that makes a difference. So, MRD testing is still not perfect. Second, we don’t have sufficient follow-up. People who are MRD-negative, even at the next-generation sequencing 10-6 level, do relapse. MRD does not equate with cure at this point. So, I think for a young person to be denied the most effective platform that has got us here for a long time would be difficult for me to forego that. And second thing, people don’t get younger and better with time. So, if you’re going to do a transplant ever, you better do it earlier.

A. Keith Stewart, MB, ChB: Spoken by a true transplanter. Noopur?

Noopur Suresh Raje, MD: I have plenty of people in my practice who I will not transplant. There are folks where I would suggest—where I’m worried about how they’re going to relapse, with renal disease, for example—transplant may be off the table for those. Those are the ones I am going to encourage to get transplanted, including the high-risk ones. But there are certain standard-risk ones, as long as I’ve collected those cells, I’m quite comfortable watching. I do worry about the older ones I’m watching, 65 to 66, because, as you pointed out, Hari, they’re not getting any younger. And I’d rather get them transplanted and move on.

A. Keith Stewart, MB, ChB: Christina?

Cristina Gasparetto, MD: I think a little bit like Hari. I think it’s still very important. The MRD is our goal, and the number of patients achieving a deeper response is higher with transplant. So, outside of a clinical trial, where we’re not testing, we know with transplant that we achieve a deeper response, so I go there aggressively.

A. Keith Stewart, MB, ChB: Bob, you sticking with your original hypothesis?

Robert Orlowski, MD, PhD: I am. Now, Hari does bring up a good point. When I mentioned MRD, I meant 10-6. It may be interesting to save a sample of the bone marrow and peripheral blood on patients for future testing, like next-generation sequencing. And we’re not denying the patient a transplant. We’re certainly just giving them an option of transplant now versus transplant later. And we know from a number of studies that second-line transplant is just as effective, especially in a younger patient. I agree that if you’ve got somebody who’s pushing 70, you probably don’t want to wait. But the other benefits are they have a better quality of life without transplant and they have a lower risk of second primary malignancies in many studies. So, those are not things to be ignored.

Parameswaran Hari, MD, MRCP, MS: Yes, I completely agree. For the community, the sad part is that only about 35% of patients who are below the age of 70 in the United States actually get to a transplant center. And I think it’s important that collection and holding at the very minimum is something that we should do in all our young patients.

Transcript Edited for Clarity 
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