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Managing Relapsed Disease 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: Monday, Feb 22, 2016


Transcript:

Keith Stewart, MB, CHB:
Let's move on to relapsed disease. I'll start with my own experience. I found more and more that I don't wait. A patient's in a complete remission, I’ve been very happy for a couple of years, and then suddenly I start to see the light chain reappearing, monoclonal protein re-level. In the old days, I would have watched that for months or even, you know, sometimes a year before we started treating, gambling a little bit that we'd be there before anything bad happened.

I find myself more and more just saying, let's just start re-treatment because we can get you back into CR quickly. Is that other people's experience or do you feel that you still have a period of where watchful waiting is appropriate? And maybe, Sagar, you start us this time.

Sagar Lonial, MD: Yeah. I think to me it really depends on how the patient presented initially. If they had high-risk disease, absolutely. If they had sort of explosive presentation with renal failure, yes. But for the most part I'm still watching and waiting and trying to get a sense for tempo. And I may not wait for the hemoglobin to get less than 10 or the creatinine to go up to 1.8. But certainly if I see the hemoglobin drifting from 12 to 11-1/2, that may be when I intervene.

Ajai Chari, MD: It may be helpful for community oncologists to think about what we use for clinical trial eligibility as a guide as well, an M-spike of 1.0 for IgG or .5 for IgA, a light chain of greater than 100. Because then, at least, if you change therapy you know what you're doing. But if your M-spike is .3 and you're adding a new agent, and next month it's .2 and then it goes back to .3, are you really gaining anything? So I think there needs to be some measurable disease or something to follow to change therapy.

Jatin J. Shah, MD: I agree. I think they each have one measurement going up. I think you have to have a couple of serial measurements saying that you're continuously going up, and I think, in that case, when you have that type of relapse, then I think it's reasonable to start as opposed to waiting until you have clinical progression. But I think [it has been] previously shown that there's another third of patients who have this slow relapse and then they'll plateau out, and then they'll plateau out again for another two years before they need therapy. So I think we have to be careful about starting therapy right away in some of these patients, because there's about 30% of patients that will have a slight rise, but then they'll kind of plateau out again for a long period of time.

Paul G. Richardson, MD: I think that very much depends also, Jatin, on what they're on. I think a patient who's maintained, who's progressing, is a different person from someone who's unmaintained.

Jatin J. Shah, MD: Yes.

Paul G. Richardson, MD: And I think the data support that. And I think that a person who's maintained and who is progressing by chemically, I completely agree, you can afford to sort of watch and wait.

Keith Stewart, MB, CHB: In that patient, Paul, would you increase the lenalidomide dose or would you switch therapy?

Paul G. Richardson, MD: That's a great question. It very much depends. When a patient said, look, why don't we just try and increase the lenalidomide and see what happens, I've certainly supported that. But to your point, I like your style here, Keith, in saying that you know smolders is sort of innocent until proven guilty. Relapse is guilty until proven innocent. And I think you know you have to think of it in those terms. So I agree with you, yeah.

Keith Stewart, MB, CHB: So you're more inclined to treat?

Paul G. Richardson, MD: More inclined to evaluate.

Keith Stewart, MB, CHB: Than in the past.

Paul G. Richardson, MD: Exactly. To evaluate. Because it gets back to what we talked about much earlier, clonal heterogeneity and the clonal tiding, which is another phenomenology. A couple of anecdotal experiences have really sort of how they frame your practice. You know when you're watching a patient and they come back a month later and they're in real trouble, those kind of experiences crystalize why we must be very careful.
                                                                                                                                                                                                                                                                                                              
Transcript Edited for Clarity
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Transcript:

Keith Stewart, MB, CHB:
Let's move on to relapsed disease. I'll start with my own experience. I found more and more that I don't wait. A patient's in a complete remission, I’ve been very happy for a couple of years, and then suddenly I start to see the light chain reappearing, monoclonal protein re-level. In the old days, I would have watched that for months or even, you know, sometimes a year before we started treating, gambling a little bit that we'd be there before anything bad happened.

I find myself more and more just saying, let's just start re-treatment because we can get you back into CR quickly. Is that other people's experience or do you feel that you still have a period of where watchful waiting is appropriate? And maybe, Sagar, you start us this time.

Sagar Lonial, MD: Yeah. I think to me it really depends on how the patient presented initially. If they had high-risk disease, absolutely. If they had sort of explosive presentation with renal failure, yes. But for the most part I'm still watching and waiting and trying to get a sense for tempo. And I may not wait for the hemoglobin to get less than 10 or the creatinine to go up to 1.8. But certainly if I see the hemoglobin drifting from 12 to 11-1/2, that may be when I intervene.

Ajai Chari, MD: It may be helpful for community oncologists to think about what we use for clinical trial eligibility as a guide as well, an M-spike of 1.0 for IgG or .5 for IgA, a light chain of greater than 100. Because then, at least, if you change therapy you know what you're doing. But if your M-spike is .3 and you're adding a new agent, and next month it's .2 and then it goes back to .3, are you really gaining anything? So I think there needs to be some measurable disease or something to follow to change therapy.

Jatin J. Shah, MD: I agree. I think they each have one measurement going up. I think you have to have a couple of serial measurements saying that you're continuously going up, and I think, in that case, when you have that type of relapse, then I think it's reasonable to start as opposed to waiting until you have clinical progression. But I think [it has been] previously shown that there's another third of patients who have this slow relapse and then they'll plateau out, and then they'll plateau out again for another two years before they need therapy. So I think we have to be careful about starting therapy right away in some of these patients, because there's about 30% of patients that will have a slight rise, but then they'll kind of plateau out again for a long period of time.

Paul G. Richardson, MD: I think that very much depends also, Jatin, on what they're on. I think a patient who's maintained, who's progressing, is a different person from someone who's unmaintained.

Jatin J. Shah, MD: Yes.

Paul G. Richardson, MD: And I think the data support that. And I think that a person who's maintained and who is progressing by chemically, I completely agree, you can afford to sort of watch and wait.

Keith Stewart, MB, CHB: In that patient, Paul, would you increase the lenalidomide dose or would you switch therapy?

Paul G. Richardson, MD: That's a great question. It very much depends. When a patient said, look, why don't we just try and increase the lenalidomide and see what happens, I've certainly supported that. But to your point, I like your style here, Keith, in saying that you know smolders is sort of innocent until proven guilty. Relapse is guilty until proven innocent. And I think you know you have to think of it in those terms. So I agree with you, yeah.

Keith Stewart, MB, CHB: So you're more inclined to treat?

Paul G. Richardson, MD: More inclined to evaluate.

Keith Stewart, MB, CHB: Than in the past.

Paul G. Richardson, MD: Exactly. To evaluate. Because it gets back to what we talked about much earlier, clonal heterogeneity and the clonal tiding, which is another phenomenology. A couple of anecdotal experiences have really sort of how they frame your practice. You know when you're watching a patient and they come back a month later and they're in real trouble, those kind of experiences crystalize why we must be very careful.
                                                                                                                                                                                                                                                                                                              
Transcript Edited for Clarity
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