Consolidation Strategies in AML Treatment

Transcript:Ruben A. Mesa, MD, FACP: So we’ve induced the patient. Hopefully, we’ve had them achieve a good response or clearly no visible disease. We’ll get around to the concept of minimal residual disease (MRD) after we talk about the next topic, which is consolidation. At the current time, what would you view, Elias, as our standard consolidation, or some of the thought processes in terms of consolidation choices?

Elias Jabbour, MD: Well, Ruben, you induce somebody and induce a CR. You mentioned you want to talk about MRD, but CR doesn’t mean cured. It doesn’t mean the leukemia is gone. It doesn’t mean nothing is happening. Although, then you have the tendency not to give a lot of consolidation.

So at my institution, we give at least four courses of high-dose ara-C consolidation. And then, based on your prognostic factor from the beginning, if you have somebody responding with bad features, today the standard of care is to go for transplant. Although, the way we do it, it’s not the best way. We have to be more innovative and give conditioning, transplant, and go for major strategy post transplantation—implement the new treatment we have into the conditioning and post transplantation.

So somebody in a good response and having no minimal disease and good features like CBF (core binding factor), we go for consolidation chemotherapy. In somebody who is young who is responding but has bad features, we do consolidation, one or two courses to get them ready for transplantation, and go for transplantation. Now, in elderly people who are not fit for transplantation, you need to keep them on therapy. And we don’t know for how long.

You give them decitabine or azacitidine. For how long? For a year? For six years? Today, the strategy is to give them treatment all along. You mentioned at the beginning the FLT3 inhibitors, and these compounds, you give them only for induction. Does it matter to give it continuously? I think it does. In our treatment, we did it a few days at the beginning and then consolidation. But now we think they may benefit more from continuous exposure, provided you can get the drug. All along, induction, consolidation, and maybe maintenance treatment, as well.

Rami S. Komrokji, MD: So our approach for the consolidation, as you mentioned, is looking at allogeneic stem cell transplant versus high-dose chemotherapy. Now, even if you have an allogeneic stem cell transplant ready, you could argue that somebody who has complete remission can proceed to allogeneic stem cell transplant. Most of the time in real life that’s not the scenario we see.

First, patients are recovering and need to wait. Transplant usually is not ready in two, three months. So we end up doing a few cycles of chemotherapy to take them to transplant. The other thing that’s evolving now is, if you are deciding just to do intensive high-dose ara-C, for example, how many cycles do you need? It had been established in the good risk. I think everybody follows the CALGB study with four cycles. But the other thing that was evolving is, what is the optimal dose of the high-dose ara-C? We’ve typically done the high-dose, 3 grams. But there are studies coming suggesting that you need that only in patients with good risk while you could do well with a moderate dose, intermediate dose, of ara-C in the group that doesn’t have the good-risk cytogenetics.

Ruben A. Mesa, MD, FACP: Now, in this process, there clearly is interest in a variety of areas in this concept of MRD. And perhaps most relevant in this group of patients in which we’ve completed consolidation, we’re hopeful that they have very minimal disease and we’re observing them. Because obviously we’ve selecting out, as we’ve discussed, many patients to move on to transplant based on their risk. Where do you think MRD stands, particularly in the setting of AML? How relevant is this concept yet for us?

Rafael Bejar MD, PhD: Now, I’d remind you that we typically look for minimal residual disease by the means that we have available. So we do a bone marrow biopsy after first course of induction to see if there’s any disease remaining, and if there, is we often treat again to go for that CR. Now, that’s a relatively crude technique that just looks for the morphologic presence or flow presence of these cells.

But we can go much deeper now that we have better flow cytometry techniques and better genetic techniques to try to find those subclones that we can’t see under the microscope. Now, it’s worked extremely well in disorders where you know what the mutation that caused the disorder is, and you can look for that. So, APL is a great example where minimal residual disease monitoring makes a big difference. You have to treat more intensively if you find that there is residual disease after that first course of therapy.

Now, in things like standard non-APL AML with normal cytogenetics, you can’t look at karyotype to look for minimal residual disease. And flow cytometry techniques have been useful, but the mutation testing may actually be even more sensitive. There was a very interesting paper that was recently published in JAMA where they looked for the presence of mutations at day 30 after treatment and found that patients that still had mutations at a low level were certainly at increased risk of relapse, and it was a substantial difference. So, while this hasn’t yet entered standard of care for normal cytogenetic—risk AML, it’s something that will probably move rapidly and begin to reach clinical practice.

Transcript Edited for Clarity