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Consolidation and Maintenance Therapy in Multiple Myeloma

Panelists:Ajai Chari, MD, Mount Sinai Hospital; Sagar Lonial, MD, Emory University School of Medicine; Paul G. Richardson, MD, Harvard Medical School; Jatin J. Shah, MD, MD Anderson Cancer Center; Keith Stewart, MD, CHB, Mayo Clinic
Published: Tuesday, Feb 16, 2016


Transcript:

Keith Stewart, MB, CHB:
I want to very briefly touch on consolidation and maintenance. Is everybody using consolidation if their patient is not in complete remission after transplant or are you going straight to lenalidomide maintenance? What do you do?

Sagar Lonial, MD: So the only people we formally do consolidation on are the high risk.

Keith Stewart, MB, CHB: By consolidation we mean more RVD-based.

Sagar Lonial, MD: Yeah, on the 3-week cycle, as opposed to our maintenance schedule, which is a 4-week cycle, or the 414's, who we give single agent bortezomib to.

Keith Stewart, MB, CHB: 414 being a high-risk subgroup of myeloma?

Sagar Lonial, MD: Yeah, we give them two cycles of RVD consolidation before we go to bortezomib maintenance.

Keith Stewart, MB, CHB: Anybody do anything differently? I must say I've not formally adopted routine consolidation. I'm sort of [considering it] patient by patient. You know some of them I think for sure they should have some. Some of them I'm like, oh you can go straight to maintenance, but I don't know if I'm right or not.

Jatin J. Shah, MD: I agree. I think that it's more of a risk-adapted approach to those patients. Maybe not who are still in a partial remission, you may want to give a little bit more consolidation therapy. But I think, in general, it's more of a risk-adapted approach.

Sagar Lonial, MD: But those are rare when you think about it.

Jatin J. Shah, MD: They are.

Sagar Lonial, MD: I mean most of the data for consolidation comes from European trials where they used a doublet up front. They didn't use a triplet.

Jatin J. Shah, MD: I agree.

Sagar Lonial, MD: And very few of our patients are not in VGPR better after a transplant. I mean at least in our experience.

Ajai Chari, MD: I agree.

Jatin J. Shah, MD: So it's really a minority of patients, I agree.

Keith Stewart, MB, CHB: That brings me to the question of minimal residual disease, interestingly enough. And so when you talk about CR after transplant, you're talking about looks okay under the microscope, or are you talking about by one million genomic sequences you don't find any? What's your practice?

Ajai Chari, MD: I think as our treatments are getting better, we can't be using the old methods of evaluation, so we can't be using, for example, quantitative immunoglobulin, so we moved past immunofixation. So, if you're now going to add very efficacious and expensive new agents, there needs to be proof of improved outcomes. So we need to improve our depth of remission assessment. And I think the problem is, is it standardized in a way that a community oncologist could know what to do with the results? And I don't think we're there yet. And as somebody brought up the other day at a meeting, you know what a hemoglobin of 8 means anywhere you go in the world. When you get MRD-negative, particularly by flow, how many events you count, how long it took the marrow to get the processing facility, how many channels were tested. It's really hodge-podge.

Keith Stewart, MB, CHB: Are you saying you think a community oncologist or somebody who's not in a major academic center, should they be sending bone marrows for post-cytometry or molecular testing or not yet, to be practical?

Sagar Lonial, MD: I don't think we know what to do with it yet, to be honest with you. I mean it's an interesting piece of information. Many patients are asking for it. But I don't feel like we have the data to act on it yet.

Paul G. Richardson, MD: I agree with Sagar. I think MRD is an incredibly important thing for the future, but right now I'm very careful. Again, dependent critically on what's assessed too. The absence of appropriate radiological screening is really relevant obviously. I go back to one point though, Keith, about this issue of consolidation and maintenance. I think an adaptive approach makes sense. I will say though in our own center we're kind of very guided by the data that supports it, and also protocol.

So we do offer consolidation. What tends to stop us is, actually, toxicology. In other words, side-effect profiles that may be an issue that make consolidation worse. We're very impressed because we're lucky enough to sort of get looks at data from our French partners. And suffice it to say, the caveats of these tools are obviously early, but certainly from the caveat of complete response, it does seem that consistently consolidation is making a difference. And that's one of the messages we'll hear at this meeting from Michel Attal, is that the consolidation piece does make a difference and certainly from the point of view of MRD testing.

Keith Stewart, MB, CHB: Just because I'm curious, patients don't feel pretty good for the first 60 days or so after transplant. When do you start them back on consolidation?

Paul G. Richardson, MD: Great question. The consolidation starts beyond day 60, and you've got a window out to day 120, and obviously as Ajai and Sagar knows, and so does Jatin, because we're all part of the trial, you've got latitude.

Sagar Lonial, MD: Paul, I guess the question I would have is we know that responses continue to deepen after transplant.

Paul G. Richardson, MD: Yes.

Sagar Lonial, MD: Even between three and six months, post-autologous transplant.

Paul G. Richardson, MD: Yes.

Sagar Lonial, MD: So, what you may be claiming credit for consolidation for may be the natural clearance of the disease.

Paul G. Richardson, MD: True. I think having said that, from some of the randomized studies from Europe, the suggestion is that the consolidation matters.

Ajai Chari, MD: And also to that point is the duration of lenalidomide maintenance as well, right?

Paul G. Richardson, MD: Right.

Ajai Chari, MD: So if you're going to have a late response in transplant, and you're using lenalidomide to progression, as opposed to stopping at one year, what is the role of consolidation in that, then?

Keith Stewart, MB, CHB: So, I'm going to take this off, just kind of wrap up for where we've been the last 10, 15 minutes. So I hear VRD for most, KRD for some selected patients. Time limited but we want a deep response, but don't go on forever before you refer them for transplant.

Paul G. Richardson, MD: That's right.

Keith Stewart, MB, CHB: Most patients go for transplant, if they can make it. The consensus seems to be building that everybody needs some form of maintenance. Consolidation is a new investigational tool, but appears to be successful and early-going. And that the consensus of the group is really lenalidomide maintenance, at least until progression, and then I think, although we didn't talk about it, most of us would concur that in a higher risk patient we would maintain a proteasome inhibitor as well.

Paul G. Richardson, MD: I would agree. Again, build from Sagar's work and others. And my only other point would be that the importance of a randomized trial. For patients who are interested in participating in a protocol, we'd really welcome the referrals. We have almost 60 centers across the country. We still have 120 patients to enroll. Because I think it's terribly important that we have a US-based trial that guides US practice. Because whilst we have the highest degree of respect for partners overseas, practice patterns are different and we must have results that are applied to the US population. In particular, this issue of maintenance until progression
                                                                                                                                                                                                                                                                                                                
Transcript Edited for Clarity
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Transcript:

Keith Stewart, MB, CHB:
I want to very briefly touch on consolidation and maintenance. Is everybody using consolidation if their patient is not in complete remission after transplant or are you going straight to lenalidomide maintenance? What do you do?

Sagar Lonial, MD: So the only people we formally do consolidation on are the high risk.

Keith Stewart, MB, CHB: By consolidation we mean more RVD-based.

Sagar Lonial, MD: Yeah, on the 3-week cycle, as opposed to our maintenance schedule, which is a 4-week cycle, or the 414's, who we give single agent bortezomib to.

Keith Stewart, MB, CHB: 414 being a high-risk subgroup of myeloma?

Sagar Lonial, MD: Yeah, we give them two cycles of RVD consolidation before we go to bortezomib maintenance.

Keith Stewart, MB, CHB: Anybody do anything differently? I must say I've not formally adopted routine consolidation. I'm sort of [considering it] patient by patient. You know some of them I think for sure they should have some. Some of them I'm like, oh you can go straight to maintenance, but I don't know if I'm right or not.

Jatin J. Shah, MD: I agree. I think that it's more of a risk-adapted approach to those patients. Maybe not who are still in a partial remission, you may want to give a little bit more consolidation therapy. But I think, in general, it's more of a risk-adapted approach.

Sagar Lonial, MD: But those are rare when you think about it.

Jatin J. Shah, MD: They are.

Sagar Lonial, MD: I mean most of the data for consolidation comes from European trials where they used a doublet up front. They didn't use a triplet.

Jatin J. Shah, MD: I agree.

Sagar Lonial, MD: And very few of our patients are not in VGPR better after a transplant. I mean at least in our experience.

Ajai Chari, MD: I agree.

Jatin J. Shah, MD: So it's really a minority of patients, I agree.

Keith Stewart, MB, CHB: That brings me to the question of minimal residual disease, interestingly enough. And so when you talk about CR after transplant, you're talking about looks okay under the microscope, or are you talking about by one million genomic sequences you don't find any? What's your practice?

Ajai Chari, MD: I think as our treatments are getting better, we can't be using the old methods of evaluation, so we can't be using, for example, quantitative immunoglobulin, so we moved past immunofixation. So, if you're now going to add very efficacious and expensive new agents, there needs to be proof of improved outcomes. So we need to improve our depth of remission assessment. And I think the problem is, is it standardized in a way that a community oncologist could know what to do with the results? And I don't think we're there yet. And as somebody brought up the other day at a meeting, you know what a hemoglobin of 8 means anywhere you go in the world. When you get MRD-negative, particularly by flow, how many events you count, how long it took the marrow to get the processing facility, how many channels were tested. It's really hodge-podge.

Keith Stewart, MB, CHB: Are you saying you think a community oncologist or somebody who's not in a major academic center, should they be sending bone marrows for post-cytometry or molecular testing or not yet, to be practical?

Sagar Lonial, MD: I don't think we know what to do with it yet, to be honest with you. I mean it's an interesting piece of information. Many patients are asking for it. But I don't feel like we have the data to act on it yet.

Paul G. Richardson, MD: I agree with Sagar. I think MRD is an incredibly important thing for the future, but right now I'm very careful. Again, dependent critically on what's assessed too. The absence of appropriate radiological screening is really relevant obviously. I go back to one point though, Keith, about this issue of consolidation and maintenance. I think an adaptive approach makes sense. I will say though in our own center we're kind of very guided by the data that supports it, and also protocol.

So we do offer consolidation. What tends to stop us is, actually, toxicology. In other words, side-effect profiles that may be an issue that make consolidation worse. We're very impressed because we're lucky enough to sort of get looks at data from our French partners. And suffice it to say, the caveats of these tools are obviously early, but certainly from the caveat of complete response, it does seem that consistently consolidation is making a difference. And that's one of the messages we'll hear at this meeting from Michel Attal, is that the consolidation piece does make a difference and certainly from the point of view of MRD testing.

Keith Stewart, MB, CHB: Just because I'm curious, patients don't feel pretty good for the first 60 days or so after transplant. When do you start them back on consolidation?

Paul G. Richardson, MD: Great question. The consolidation starts beyond day 60, and you've got a window out to day 120, and obviously as Ajai and Sagar knows, and so does Jatin, because we're all part of the trial, you've got latitude.

Sagar Lonial, MD: Paul, I guess the question I would have is we know that responses continue to deepen after transplant.

Paul G. Richardson, MD: Yes.

Sagar Lonial, MD: Even between three and six months, post-autologous transplant.

Paul G. Richardson, MD: Yes.

Sagar Lonial, MD: So, what you may be claiming credit for consolidation for may be the natural clearance of the disease.

Paul G. Richardson, MD: True. I think having said that, from some of the randomized studies from Europe, the suggestion is that the consolidation matters.

Ajai Chari, MD: And also to that point is the duration of lenalidomide maintenance as well, right?

Paul G. Richardson, MD: Right.

Ajai Chari, MD: So if you're going to have a late response in transplant, and you're using lenalidomide to progression, as opposed to stopping at one year, what is the role of consolidation in that, then?

Keith Stewart, MB, CHB: So, I'm going to take this off, just kind of wrap up for where we've been the last 10, 15 minutes. So I hear VRD for most, KRD for some selected patients. Time limited but we want a deep response, but don't go on forever before you refer them for transplant.

Paul G. Richardson, MD: That's right.

Keith Stewart, MB, CHB: Most patients go for transplant, if they can make it. The consensus seems to be building that everybody needs some form of maintenance. Consolidation is a new investigational tool, but appears to be successful and early-going. And that the consensus of the group is really lenalidomide maintenance, at least until progression, and then I think, although we didn't talk about it, most of us would concur that in a higher risk patient we would maintain a proteasome inhibitor as well.

Paul G. Richardson, MD: I would agree. Again, build from Sagar's work and others. And my only other point would be that the importance of a randomized trial. For patients who are interested in participating in a protocol, we'd really welcome the referrals. We have almost 60 centers across the country. We still have 120 patients to enroll. Because I think it's terribly important that we have a US-based trial that guides US practice. Because whilst we have the highest degree of respect for partners overseas, practice patterns are different and we must have results that are applied to the US population. In particular, this issue of maintenance until progression
                                                                                                                                                                                                                                                                                                                
Transcript Edited for Clarity
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