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Role of Consolidation Therapy in Myeloma

Panelists: A. Keith Stewart, MB, ChB, The Mayo Clinic in Phoenix Arizona; Thomas Martin, MD, UCSF Helen Diller Family Comprehensive Cancer Center; Faith Davies, MD, MBBCh, MRCP, FRCPath, University of Arkansas for Medical Sciences; Rafael Fonseca, MD, The Mayo Clinic in Phoenix Arizona; Adriana Rossi, MD, Weill Cornell Medical College
Published: Wednesday, Feb 13, 2019



Transcript:

A. Keith Stewart, MB, ChB:
We’ve talked about induction a lot. We’ve touched on transplant. We’ve talked about MRD [minimal residual disease] negativity. What about consolidation therapy? So you’ve got it good but are not in complete remission [CR] after initial therapy perhaps, particularly in the elderly. How do you watch consolidation therapy? Are you going to escalate treatment at that point, Tom?

Thomas Martin, MD: Well you say, “in the elderly.” In the elderly I’m not usually doing any form of consolidation-based therapy. They get their 3-drug regimen for anywhere between 8 and 12 months to get their initial response. And then after that I’m trying to pick the 2, or 1 or 2 drugs, that are the best tolerated, and continue on it in that group.

A. Keith Stewart, MB, ChB: What about for the younger patient?

Thomas Martin, MD: We have some controversy, obviously. The EMN [European Myeloma Network] trial from Europe, where they did not use a PI [proteasome inhibitor] and an IMiD [immunomodulatory drug] as induction therapy, showed that consolidation therapy using an IMiD has perhaps some improvement in PFS [progression-free survival]. However, in the US study, the StaMINA trial, where the majority of patients received a PI plus an IMiD as induction therapy, there really was no benefit to consolidation post-autologous transplant.

A. Keith Stewart, MB, ChB: What’s your opinion? Let’s get practical here.

Thomas Martin, MD: I would say that really depends, for the younger patient, on how much improvement in their disease burden they’ve had. If they get induction therapy at transplant and they still have measurable disease, then yes, I would give them consolidation to push their disease down further. And I would change if it was RVd [lenalidomide/bortezomib/dexamethasone]/transplant, and they’re still in PR [partial response] or they’re in VGPR [very good partial response], I’m going to give them KRd [carfilzomib/lenalidomide/dexamethasone] for a few cycles to try to get them to that low point and then put them on maintenance.

A. Keith Stewart, MB, ChB: This seems to be the trend. We used to give hit and run therapy, or 4 months of treatment at transplant and we’d stop. There’s usually more and more of a trend to treat for longer. Adriana, what was the right duration of consolidation and maintenance therapy? What do you think?

Adriana Rossi, MD: I would love to answer that. My answer is, it depends. My goal in a transplant eligible patient is to get them to that MRD-negative state. If I can do it with an induction, I may defer a transplant. If I do it with an induction and a transplant, I will certainly maintain. If the induction and transplant doesn’t get me there, I do start a second triplet, and it may actually be KPd [carfilzomib/pomalidomide/dexamethasone] if VRd didn’t do it, to try to get them to that MRD-negative place.

A. Keith Stewart, MB, ChB: I must say that I differ from my colleague, Rafael. I don’t do a day-100 MRD test, because I’m pretty much giving everybody consolidation, so I don’t see any point in doing it at 100 days, because it’s not going to change. I’m going to give them consolidation anyway, so I’ll wait until after that before I even test.

Thomas Martin, MD: How many cycles of consolidation do you give in that setting?

A. Keith Stewart, MB, ChB: Four, usually. And then I test. Maybe 6. You know, transplant, 4 more cycles, and then I’ll test and see how much further I’d go.

Rafael Fonseca, MD: Here’s a suggestion because sometimes MRD has some quantity aspects to it. You could measure and if it’s positive and you use consolidation, you can engage for your consolidation to work versus not; because they may be meaning the self-clinical level. So they may mean a CR with 100 cells. You give them a direct combination, they come back and they’re 150 cells.

A. Keith Stewart, MB, ChB: But if your patient is MRD-negative at day 100, are you not going to do anything?

Rafael Fonseca, MD: No, no, but what if they’re positive? If they’re negative I’m still going to go with a consolidation. In fact, one of the points I was going to make is semantics, right? There are trials that are designed to test a consolidation, like the BMT CTN [Blood and Marrow Transplant Clinical Trials Network] trial. It has these 4 VRds post-transplant. But then we have the trial that we have referenced now 3 times. That actually was consolidation post-transplant. The KRd/transplant, then more KRd. So in short I’m doing consolidation, but I do like to know where we start, and we’re doing the testing once a year for the MRD just to gauge where we are.  

A. Keith Stewart, MB, ChB: So we’re getting real close to total therapy here.

Faith Davies, MD, MBBCh, MRCP, FRCPath: I’d like to take Tom’s idea a little bit further. Because I think one of the things, if you think of it from a biological perspective, one of the things that consolidation can do is if you change up a little bit, your assumption is that you’ve maybe got some stray cells. They didn’t respond, those stray cells, to your induction therapy and your transplant. And so presumably they may be resistant to whatever you used. So changing up your consolidation a little bit I think is important.

Transcript edited for clarity.

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Transcript:

A. Keith Stewart, MB, ChB:
We’ve talked about induction a lot. We’ve touched on transplant. We’ve talked about MRD [minimal residual disease] negativity. What about consolidation therapy? So you’ve got it good but are not in complete remission [CR] after initial therapy perhaps, particularly in the elderly. How do you watch consolidation therapy? Are you going to escalate treatment at that point, Tom?

Thomas Martin, MD: Well you say, “in the elderly.” In the elderly I’m not usually doing any form of consolidation-based therapy. They get their 3-drug regimen for anywhere between 8 and 12 months to get their initial response. And then after that I’m trying to pick the 2, or 1 or 2 drugs, that are the best tolerated, and continue on it in that group.

A. Keith Stewart, MB, ChB: What about for the younger patient?

Thomas Martin, MD: We have some controversy, obviously. The EMN [European Myeloma Network] trial from Europe, where they did not use a PI [proteasome inhibitor] and an IMiD [immunomodulatory drug] as induction therapy, showed that consolidation therapy using an IMiD has perhaps some improvement in PFS [progression-free survival]. However, in the US study, the StaMINA trial, where the majority of patients received a PI plus an IMiD as induction therapy, there really was no benefit to consolidation post-autologous transplant.

A. Keith Stewart, MB, ChB: What’s your opinion? Let’s get practical here.

Thomas Martin, MD: I would say that really depends, for the younger patient, on how much improvement in their disease burden they’ve had. If they get induction therapy at transplant and they still have measurable disease, then yes, I would give them consolidation to push their disease down further. And I would change if it was RVd [lenalidomide/bortezomib/dexamethasone]/transplant, and they’re still in PR [partial response] or they’re in VGPR [very good partial response], I’m going to give them KRd [carfilzomib/lenalidomide/dexamethasone] for a few cycles to try to get them to that low point and then put them on maintenance.

A. Keith Stewart, MB, ChB: This seems to be the trend. We used to give hit and run therapy, or 4 months of treatment at transplant and we’d stop. There’s usually more and more of a trend to treat for longer. Adriana, what was the right duration of consolidation and maintenance therapy? What do you think?

Adriana Rossi, MD: I would love to answer that. My answer is, it depends. My goal in a transplant eligible patient is to get them to that MRD-negative state. If I can do it with an induction, I may defer a transplant. If I do it with an induction and a transplant, I will certainly maintain. If the induction and transplant doesn’t get me there, I do start a second triplet, and it may actually be KPd [carfilzomib/pomalidomide/dexamethasone] if VRd didn’t do it, to try to get them to that MRD-negative place.

A. Keith Stewart, MB, ChB: I must say that I differ from my colleague, Rafael. I don’t do a day-100 MRD test, because I’m pretty much giving everybody consolidation, so I don’t see any point in doing it at 100 days, because it’s not going to change. I’m going to give them consolidation anyway, so I’ll wait until after that before I even test.

Thomas Martin, MD: How many cycles of consolidation do you give in that setting?

A. Keith Stewart, MB, ChB: Four, usually. And then I test. Maybe 6. You know, transplant, 4 more cycles, and then I’ll test and see how much further I’d go.

Rafael Fonseca, MD: Here’s a suggestion because sometimes MRD has some quantity aspects to it. You could measure and if it’s positive and you use consolidation, you can engage for your consolidation to work versus not; because they may be meaning the self-clinical level. So they may mean a CR with 100 cells. You give them a direct combination, they come back and they’re 150 cells.

A. Keith Stewart, MB, ChB: But if your patient is MRD-negative at day 100, are you not going to do anything?

Rafael Fonseca, MD: No, no, but what if they’re positive? If they’re negative I’m still going to go with a consolidation. In fact, one of the points I was going to make is semantics, right? There are trials that are designed to test a consolidation, like the BMT CTN [Blood and Marrow Transplant Clinical Trials Network] trial. It has these 4 VRds post-transplant. But then we have the trial that we have referenced now 3 times. That actually was consolidation post-transplant. The KRd/transplant, then more KRd. So in short I’m doing consolidation, but I do like to know where we start, and we’re doing the testing once a year for the MRD just to gauge where we are.  

A. Keith Stewart, MB, ChB: So we’re getting real close to total therapy here.

Faith Davies, MD, MBBCh, MRCP, FRCPath: I’d like to take Tom’s idea a little bit further. Because I think one of the things, if you think of it from a biological perspective, one of the things that consolidation can do is if you change up a little bit, your assumption is that you’ve maybe got some stray cells. They didn’t respond, those stray cells, to your induction therapy and your transplant. And so presumably they may be resistant to whatever you used. So changing up your consolidation a little bit I think is important.

Transcript edited for clarity.
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