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Upfront Therapy Approaches 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: Tuesday, Jan 30, 2018



Transcript: 

A. Keith Stewart, MB, ChB: Let’s move on to talk about treatment of patients who have active myeloma by conventional criteria. And maybe we’ll ask you, Hari, to kick this off. How do you treat your newly diagnosed patient today? Let’s define that as with a younger patient.

Parameswaran Hari, MD, MRCP, MS: So, for a newly diagnosed younger patient, almost always we should think about a transplant-based strategy to get them into a deep remission as quickly as possible. Outside of a clinical trial, I would still recommend a 3-drug induction with bortezomib/lenalidomide/dexamethasone. Sometimes there are exceptions. If a patient has renal failure or cannot get lenalidomide on time because of insurance issues, which are practical issues in the United States only, they need to go on a 3-drug induction with cyclophosphamide substituting for lenalidomide and then switch over to lenalidomide as soon as possible. If they don’t really get a good response within the first 3 to 4 cycles, I tend to do a little bit of a response adapted therapy, especially for those patients who I think need to get to a really good remission.

A. Keith Stewart, MB, ChB: And what would you do then?

Parameswaran Hari, MD, MRCP, MS: I would then switch over to a carfilzomib-based regimen, a KRd regimen, and then take them to transplant. If they still don’t get to into a VGPR before transplant, I would just transplant them.

A. Keith Stewart, MB, ChB: Noopur, you sort of invented the VRd-lite regimen. Do you use that in your elderly patients?

Noopur Suresh Raje, MD: I do tend to use a 3-drug combination even in the older patient population. And I think it’s important that you mentioned RVd-lite. So, as long as you dose adjust, I do believe that most patients can still tolerate a triplet.

A. Keith Stewart, MB, ChB: And what about you, for the younger patient, are you using carfilzomib or bortezomib upfront?

Noopur Suresh Raje, MD: There are data with carfilzomib/lenalidomide/dexamethasone combinations. This is all phase II data and the data look pretty good. There is a head-to-head comparison of RVd and KRd also. This is the ECOG trial. We still don’t have data with that, so depending on whether one is better than the other, we may preferentially use this. But I do tend to agree with Hari because there are certain patients where you will use risk-adapted treatment, very high-risk, very young patients, and in the context of a clinical trial I have used KRd.

A. Keith Stewart, MB, ChB: So, let’s talk high risk. Bob, you come in, you have a high-risk patient, deletion 17p, t(4;14). What’s your induction strategy with that patient?

Robert Orlowski, MD, PhD: Well, I would actually push back a little bit on Hari about the transplant part of things. We have data published earlier this year, from the IFM (Francophone du Myelome) Dana Farber study on the French side, that showed that for the group that got VRd induction, had stem cells collected but didn’t go to transplant, had some VRd consolidation and then lenalidomide maintenance, if they were MRD-negative, they did just as well as the people who got to MRD negativity after a transplant. So, that would suggest, not prove, that if you’re a in the good risk group—I wouldn’t do this for high-risk people—and you get to MRD negativity, it would be reasonable to give them a choice of either harvest and hold or harvest and do the transplant. For high risk, which is what you asked, I think that’s more problematic because these are people who need a much deeper response. And I think there’s actually good rationale for proceeding with a transplant even if you’re MRD-negative there.

A. Keith Stewart, MB, ChB: I want to come back to 4-drug inductions in a second. But let’s just deal with the transplant issue. So, Bob is saying if you’re MRD-negative, you don’t need a transplant. Noopur, what do you think of that?

Noopur Suresh Raje, MD: I’m going to push back a little bit there because the MRD testing was done a little bit later. So, they had the luxury of looking back. I think it’s really important for the audience to understand that everybody needs to be collected. Somebody who’s transplant eligible, until we get this data out there, collection is really important. Withholding treatment could be all right, but that MRD negativity was at an 18-month time point, and you’re looking at transplant pretty early after 4 to 6 cycles of treatment. So, as of right now, the standard of care is still transplant if you’re transplant eligible based on the data we have.

Transcript Edited for Clarity 

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Transcript: 

A. Keith Stewart, MB, ChB: Let’s move on to talk about treatment of patients who have active myeloma by conventional criteria. And maybe we’ll ask you, Hari, to kick this off. How do you treat your newly diagnosed patient today? Let’s define that as with a younger patient.

Parameswaran Hari, MD, MRCP, MS: So, for a newly diagnosed younger patient, almost always we should think about a transplant-based strategy to get them into a deep remission as quickly as possible. Outside of a clinical trial, I would still recommend a 3-drug induction with bortezomib/lenalidomide/dexamethasone. Sometimes there are exceptions. If a patient has renal failure or cannot get lenalidomide on time because of insurance issues, which are practical issues in the United States only, they need to go on a 3-drug induction with cyclophosphamide substituting for lenalidomide and then switch over to lenalidomide as soon as possible. If they don’t really get a good response within the first 3 to 4 cycles, I tend to do a little bit of a response adapted therapy, especially for those patients who I think need to get to a really good remission.

A. Keith Stewart, MB, ChB: And what would you do then?

Parameswaran Hari, MD, MRCP, MS: I would then switch over to a carfilzomib-based regimen, a KRd regimen, and then take them to transplant. If they still don’t get to into a VGPR before transplant, I would just transplant them.

A. Keith Stewart, MB, ChB: Noopur, you sort of invented the VRd-lite regimen. Do you use that in your elderly patients?

Noopur Suresh Raje, MD: I do tend to use a 3-drug combination even in the older patient population. And I think it’s important that you mentioned RVd-lite. So, as long as you dose adjust, I do believe that most patients can still tolerate a triplet.

A. Keith Stewart, MB, ChB: And what about you, for the younger patient, are you using carfilzomib or bortezomib upfront?

Noopur Suresh Raje, MD: There are data with carfilzomib/lenalidomide/dexamethasone combinations. This is all phase II data and the data look pretty good. There is a head-to-head comparison of RVd and KRd also. This is the ECOG trial. We still don’t have data with that, so depending on whether one is better than the other, we may preferentially use this. But I do tend to agree with Hari because there are certain patients where you will use risk-adapted treatment, very high-risk, very young patients, and in the context of a clinical trial I have used KRd.

A. Keith Stewart, MB, ChB: So, let’s talk high risk. Bob, you come in, you have a high-risk patient, deletion 17p, t(4;14). What’s your induction strategy with that patient?

Robert Orlowski, MD, PhD: Well, I would actually push back a little bit on Hari about the transplant part of things. We have data published earlier this year, from the IFM (Francophone du Myelome) Dana Farber study on the French side, that showed that for the group that got VRd induction, had stem cells collected but didn’t go to transplant, had some VRd consolidation and then lenalidomide maintenance, if they were MRD-negative, they did just as well as the people who got to MRD negativity after a transplant. So, that would suggest, not prove, that if you’re a in the good risk group—I wouldn’t do this for high-risk people—and you get to MRD negativity, it would be reasonable to give them a choice of either harvest and hold or harvest and do the transplant. For high risk, which is what you asked, I think that’s more problematic because these are people who need a much deeper response. And I think there’s actually good rationale for proceeding with a transplant even if you’re MRD-negative there.

A. Keith Stewart, MB, ChB: I want to come back to 4-drug inductions in a second. But let’s just deal with the transplant issue. So, Bob is saying if you’re MRD-negative, you don’t need a transplant. Noopur, what do you think of that?

Noopur Suresh Raje, MD: I’m going to push back a little bit there because the MRD testing was done a little bit later. So, they had the luxury of looking back. I think it’s really important for the audience to understand that everybody needs to be collected. Somebody who’s transplant eligible, until we get this data out there, collection is really important. Withholding treatment could be all right, but that MRD negativity was at an 18-month time point, and you’re looking at transplant pretty early after 4 to 6 cycles of treatment. So, as of right now, the standard of care is still transplant if you’re transplant eligible based on the data we have.

Transcript Edited for Clarity 
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