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Maintenance Therapy and Treating Relapse in APL

Insights From: Elihu Estey, MD, University of Washington School of Medicine Seattle; Ehab Atallah, MD, Medical College of Wisconsin
Published: Monday, Jan 30, 2017


Transcript:

Elihu Estey, MD:
Maintenance therapy should essentially disappear for APL. Once you’re done with the 4 to 6 months, let’s say, of therapy of arsenic/ATRA, then there is no reason to continue the therapy. For many years, there was maintenance therapy and it would go on for 2 years, but as the drugs became more effective, there become less need for maintenance therapy, and that’s a general phenomenon. If the drugs that you use initially are more effective, then there’s less need for maintenance therapy.

Ehab Atallah, MD: After patients complete their treatment, both induction and consolidation, we do repeat a bone marrow biopsy to confirm that they are in remission. With that bone marrow, we also check for the PML/RARα by PCR for patients with low- or intermediate-risk disease. After that, we can continue to monitor the peripheral blood by PCR only. Given that those patients have such a low risk for relapse, peripheral blood PCR monitoring is usually adequate. However, for patients with high-risk APL, we may consider doing bone marrow biopsies and also checking for the PML/RARα by PCR. In the arsenic era, however, most of those patients, whether high risk, intermediate risk, or low risk, the chances for relapse are very, very small. So, peripheral blood monitoring by PCR is most likely adequate in all patients.

Elihu Estey, MD: Relapse at APL almost never occurs in people who present with low white blood cell counts. It may occur in 5% or 10% of people who have high white blood cell counts. The best indicator of relapse is the molecular test that is pathognomonic of APL, the so-called PML/RARα test. The molecular test generally becomes positive maybe several months before actual hematologic relapse. In people who are at risk of relapse—which is people who have high white blood cell counts, not low white blood cell counts—generally a bone marrow is obtained every 3 months. If the test becomes positive, they are considered to have molecular relapse, which inevitably translates into hematologic relapse that eventually would translate into symptomatic relapse just as in presentation. These days, the idea is you want to treat the molecular relapse. Probably another drug we developed at MD Anderson for this purpose was called Mylotarg, which is a very effective drug for APL. And so, that’s certainly one way of treating molecular relapse.

Ehab Atallah, MD: After remission, the chances for relapses are very small when patients receive upfront arsenic. In the studies that were done, the median time to relapse was about 15 months when patients received arsenic therapy, and it was a little longer than that when patients did not receive arsenic therapy up front.

Elihu Estey, MD: One of the questions that comes up is a lot depends on how long the first remission lasted. For example, if you had a remission that lasted only 5 or 6 months, then the likelihood that Mylotarg will work is the patient will go back in remission, but they will relapse again. At that point, people begin to think of doing a transplant, and that can either be an autologous transplant where a patient’s own cells you use or an allogeneic transplant where there’s a donor that’s not the patient.

Transcript Edited for Clarity
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Transcript:

Elihu Estey, MD:
Maintenance therapy should essentially disappear for APL. Once you’re done with the 4 to 6 months, let’s say, of therapy of arsenic/ATRA, then there is no reason to continue the therapy. For many years, there was maintenance therapy and it would go on for 2 years, but as the drugs became more effective, there become less need for maintenance therapy, and that’s a general phenomenon. If the drugs that you use initially are more effective, then there’s less need for maintenance therapy.

Ehab Atallah, MD: After patients complete their treatment, both induction and consolidation, we do repeat a bone marrow biopsy to confirm that they are in remission. With that bone marrow, we also check for the PML/RARα by PCR for patients with low- or intermediate-risk disease. After that, we can continue to monitor the peripheral blood by PCR only. Given that those patients have such a low risk for relapse, peripheral blood PCR monitoring is usually adequate. However, for patients with high-risk APL, we may consider doing bone marrow biopsies and also checking for the PML/RARα by PCR. In the arsenic era, however, most of those patients, whether high risk, intermediate risk, or low risk, the chances for relapse are very, very small. So, peripheral blood monitoring by PCR is most likely adequate in all patients.

Elihu Estey, MD: Relapse at APL almost never occurs in people who present with low white blood cell counts. It may occur in 5% or 10% of people who have high white blood cell counts. The best indicator of relapse is the molecular test that is pathognomonic of APL, the so-called PML/RARα test. The molecular test generally becomes positive maybe several months before actual hematologic relapse. In people who are at risk of relapse—which is people who have high white blood cell counts, not low white blood cell counts—generally a bone marrow is obtained every 3 months. If the test becomes positive, they are considered to have molecular relapse, which inevitably translates into hematologic relapse that eventually would translate into symptomatic relapse just as in presentation. These days, the idea is you want to treat the molecular relapse. Probably another drug we developed at MD Anderson for this purpose was called Mylotarg, which is a very effective drug for APL. And so, that’s certainly one way of treating molecular relapse.

Ehab Atallah, MD: After remission, the chances for relapses are very small when patients receive upfront arsenic. In the studies that were done, the median time to relapse was about 15 months when patients received arsenic therapy, and it was a little longer than that when patients did not receive arsenic therapy up front.

Elihu Estey, MD: One of the questions that comes up is a lot depends on how long the first remission lasted. For example, if you had a remission that lasted only 5 or 6 months, then the likelihood that Mylotarg will work is the patient will go back in remission, but they will relapse again. At that point, people begin to think of doing a transplant, and that can either be an autologous transplant where a patient’s own cells you use or an allogeneic transplant where there’s a donor that’s not the patient.

Transcript Edited for Clarity
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