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Maintenance Therapy for AML

Panelists: Elias Jabbour, MD, MD Anderson Cancer Center; Martin S. Tallman, MD, Memorial Sloan Kettering Cancer Center; Richard M. Stone, MD, Dana-Farber Cancer Institute; Harry Erba, MD, PhD, University of Alabama; Mark Levis, MD, PhD, Sidney Kimmel Comprehensive Cancer Center
Published: Wednesday, Jan 18, 2017


Transcript:

Elias Jabbour, MD:
Before I move to my second part, my last question to you, Richard, is, how about maintenance therapy? These patients who are MRD-positive or not who have relapsed, or they had a transplant for MRD-positivity, any role for maintenance therapy with 5-azacytidine or FLT3 inhibitors or something? What’s the role of maintenance globally??

Richard M. Stone, MD: If, by maintenance, you mean low-dose therapy after high-dose therapy is completed, I would say the answer is “no.” At the moment, we don’t really have strong data to support that. There have been some data from your institution that azacitidine maintenance may have a role, but I haven’t been convinced by that. There were data from a CALGB trial that Bill Blum just published about decitabine maintenance. It wasn’t randomized. It didn’t seem to make a huge difference compared to historical control. So, I’m not yet excited about maintenance.

Elias Jabbour, MD: So, if they’re somebody who’s young who doesn’t have a donor, and you infused them with 3+7 high-dose Ara-C consolidation, they are MRD-positive, and you don’t have a transplant option.

Richard M. Stone, MD: Well, first of all, everybody is a transplant option.

Elias Jabbour, MD: Well, you have haploid transplantation.

Richard M. Stone, MD: You’ve got haploid transplants; you can do core blood. And if I’m really concerned—again, I don’t use MRD yet—but if they have bad disease features, as was outlined earlier, I would send them for transplant.

Mark J. Levis, MD, PhD: But getting to that point, with maintenance therapy, you’re not going to get a maintenance therapy approved without really developing a standardized MRD assay. Because the regulatory agencies already basically say, “Prove to us that there is disease that you can follow and that’s the reason you’re having…”

Elias Jabbour, MD: Let’s put aside MRD assessment because we don’t have an assay. We can debate about it. Let’s say somebody had a complex karyotype, and you have a 20-gene panel, P53 mutation up front, you give them chemotherapy and they do respond, you don’t have a transplant for whatever reason—the patient is refusing transplantation, haploid transplantation—I don’t like it—would you consider a scenario where maintenance is justified, knowing that there’s no evidence of randomized trials suggesting maintenance?

Martin S. Tallman, MD: I would not be enthusiastic about maintenance, even in that setting. The lack of adequate randomized trials.

Mark J. Levis, MD, PhD: Every trial that has looked at it has failed.

Martin S. Tallman, MD: Right.

Harry P. Erba, MD, PhD: To build on one thing that Marty said, that it is pretty clear that if you ask any of us what mechanism do we have to prevent relapse, allogeneic transplant seems to have the best activity. And so, we select patients based on genotype, CBF translocations, maybe normal karyotype with nucleophosmin or biallelic CEBP-alpha mutations, to do consolidation and hold transplant in the event of relapse, mostly because of the transplant-related toxicity we’re trying to avoid in that relatively good set of patients.

But I do want to bring up an important abstract that’s being presented at this ASH 2016 meeting by John Pagel for an intergroup study led by SWOG 1203. We looked to see if we could improve the outcomes of patients with complex poor-risk karyotypes who are undergoing AML induction chemotherapy. There was a concerted effort for those patients to get HLA typing done during their remission induction therapy through the National Marrow Donor Program. Patients who achieved a remission, who had high-risk karyotype, and had the typing done then would go on to transplant. And what he’s going to present is that we were able to increase the number of patients going on to transplant in that subset of patients—up to 60% of the patients from our historical control of only 40%—and it looks like those patients may be doing better.

So, what does this mean for a practicing physician? I think if we really believe this is true, then I would advocate for getting younger patients, definitely, but maybe all, to a transplant center to get their induction chemotherapy—unless the center has the ability to do HLA typing very early.

Elias Jabbour, MD: Great.

Transcript Edited for Clarity
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Transcript:

Elias Jabbour, MD:
Before I move to my second part, my last question to you, Richard, is, how about maintenance therapy? These patients who are MRD-positive or not who have relapsed, or they had a transplant for MRD-positivity, any role for maintenance therapy with 5-azacytidine or FLT3 inhibitors or something? What’s the role of maintenance globally??

Richard M. Stone, MD: If, by maintenance, you mean low-dose therapy after high-dose therapy is completed, I would say the answer is “no.” At the moment, we don’t really have strong data to support that. There have been some data from your institution that azacitidine maintenance may have a role, but I haven’t been convinced by that. There were data from a CALGB trial that Bill Blum just published about decitabine maintenance. It wasn’t randomized. It didn’t seem to make a huge difference compared to historical control. So, I’m not yet excited about maintenance.

Elias Jabbour, MD: So, if they’re somebody who’s young who doesn’t have a donor, and you infused them with 3+7 high-dose Ara-C consolidation, they are MRD-positive, and you don’t have a transplant option.

Richard M. Stone, MD: Well, first of all, everybody is a transplant option.

Elias Jabbour, MD: Well, you have haploid transplantation.

Richard M. Stone, MD: You’ve got haploid transplants; you can do core blood. And if I’m really concerned—again, I don’t use MRD yet—but if they have bad disease features, as was outlined earlier, I would send them for transplant.

Mark J. Levis, MD, PhD: But getting to that point, with maintenance therapy, you’re not going to get a maintenance therapy approved without really developing a standardized MRD assay. Because the regulatory agencies already basically say, “Prove to us that there is disease that you can follow and that’s the reason you’re having…”

Elias Jabbour, MD: Let’s put aside MRD assessment because we don’t have an assay. We can debate about it. Let’s say somebody had a complex karyotype, and you have a 20-gene panel, P53 mutation up front, you give them chemotherapy and they do respond, you don’t have a transplant for whatever reason—the patient is refusing transplantation, haploid transplantation—I don’t like it—would you consider a scenario where maintenance is justified, knowing that there’s no evidence of randomized trials suggesting maintenance?

Martin S. Tallman, MD: I would not be enthusiastic about maintenance, even in that setting. The lack of adequate randomized trials.

Mark J. Levis, MD, PhD: Every trial that has looked at it has failed.

Martin S. Tallman, MD: Right.

Harry P. Erba, MD, PhD: To build on one thing that Marty said, that it is pretty clear that if you ask any of us what mechanism do we have to prevent relapse, allogeneic transplant seems to have the best activity. And so, we select patients based on genotype, CBF translocations, maybe normal karyotype with nucleophosmin or biallelic CEBP-alpha mutations, to do consolidation and hold transplant in the event of relapse, mostly because of the transplant-related toxicity we’re trying to avoid in that relatively good set of patients.

But I do want to bring up an important abstract that’s being presented at this ASH 2016 meeting by John Pagel for an intergroup study led by SWOG 1203. We looked to see if we could improve the outcomes of patients with complex poor-risk karyotypes who are undergoing AML induction chemotherapy. There was a concerted effort for those patients to get HLA typing done during their remission induction therapy through the National Marrow Donor Program. Patients who achieved a remission, who had high-risk karyotype, and had the typing done then would go on to transplant. And what he’s going to present is that we were able to increase the number of patients going on to transplant in that subset of patients—up to 60% of the patients from our historical control of only 40%—and it looks like those patients may be doing better.

So, what does this mean for a practicing physician? I think if we really believe this is true, then I would advocate for getting younger patients, definitely, but maybe all, to a transplant center to get their induction chemotherapy—unless the center has the ability to do HLA typing very early.

Elias Jabbour, MD: Great.

Transcript Edited for Clarity
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