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Acute Lymphoblastic Leukemia: The Future of Treatment

Panelists: Mark R. Litzow, MD, Mayo Clinic; Ryan D. Cassaday, MD, University of Washington School of Medicine; Aaron C. Logan, MD, PhD, University of California San Francisco Medical Sciences Building; Bijal D. Shah, MD, Moffitt Cancer Center; Anthony S. Stein, MD, Hematologic Malignancies and Stem Cell Transplantation Institute
Published: Monday, Apr 09, 2018



Transcript: 

Mark R. Litzow, MD: I want to thank each of you. This has been extremely informative. I appreciate your expert perspectives. I’d like to close by asking each of you to make some closing remarks. What excites you now in the field of ALL? What do you think the interesting questions are? Anthony, why don’t you start us off?

Anthony S. Stein, MD: Having taken care of ALL for the last 30 years, I think over the last 5 or 10 years, we have 3 exciting new promising agents: blinatumomab, inotuzumab, and CAR T cells. The question is going to be how to incorporate them as single agents together with chemotherapy or how to move them up into the up-front setting, where we already have a SWOG study for patients over the age of 65 with Ph-negative ALL who are only being treated with blinatumomab for 5 cycles and then going on a maintenance therapy. So, I think the results of that study will give us a lot of information about what the results of using immunotherapy are in an up-front setting. And then, we have the ECOG study randomizing patients to blinatumomab or consolidation chemotherapy. I think the goal in 5 to 10 years is hopefully to have a chemotherapy-free treatment for ALL so patients are not suffering from cardiac toxicity or neuropathy or needing treatment for 3 years at a time.

Mark R. Litzow, MD: Thank you. Aaron?

Aaron C. Logan, MD, PhD: I’m excited about a lot of things in the ALL space, one of which is the increasing awareness about measurable residual disease and ease of access to testing for it. I think every ALL patient, regardless of their age, needs to have MRD testing throughout the course of their therapy, because it can guide meaningful decisions about how to prevent that patient from relapsing and get them onto the right track. The accessibility of things like centralized labs for flow cytometry or next-generation sequencing are very, very important to enable that.

I’m excited about all of these new agents, not only because we can capture some of our relapsed/refractory patients for whom chemotherapy didn’t work but also because of this prospect that maybe we can achieve that goal of chemotherapy-free induction maintenance and consolidation and maybe eliminate transplant for even some of the high-risk patients. One of the things I find very difficult when taking care of a patient with ALL is when my adult patient says, “When can I return to work?” You’re thinking, “Well, if you do well and you stay on therapy, you’re going to be on chemotherapy for an awfully long time. And if you get a transplant, you’re going to be out of commission for an awfully long time.” I would love to get to a point where we can cure patients in the course of months and give them their lives back—let them return to work, let them return to their families—and that’s when I think we’re going to be having big impacts.

Mark R. Litzow, MD: Thank you. Ryan?

Ryan D. Cassaday, MD: Certainly, there’s a lot of excitement and optimism about the new agents and the potential power that they have. I think for me, as we get better at risk stratifying patients—both in terms of their baseline biologic features, whether it’s Ph-like or it’s RAS mutations in T-cell ALL—we’re still relying on some of those old school modalities, the cytogenetics and things like that. But then, there are better response assessments with better MRD techniques so that we can better tailor and understand who are those patients who are going to do well with the things we have now. Who do we really need to think about treating in an alternative manner, whether it’s with blinatumomab, intensified chemotherapy, transplant, or no transplant? Some of those goals I think are a little bit more in reach and something that we can get a handle on, even in the next year or two while we’re waiting for some of these bigger studies to come along and show that we can get rid of a lot of the chemotherapy and use some of these new agents.

Bijal D. Shah, MD: I think what we’re all saying is that we’re excited that we get to personalize therapy for our patients based on their biology, based on their response. We get to personalize it with nonchemotherapeutic options that have a potential to very meaningfully impact their survival. So, without a question, that’s what I’m excited about.

Mark R. Litzow, MD: Thank you. I would echo those thoughts. I think we can’t forget T-cell disease, which is still really a boondoggle around our necks, and we’re hoping that there will be further breakthroughs in that area. I think that using pediatric intensive regimens and using measurable residual disease and using immunotherapy have great potential to move us away from the amount of chemotherapy that we have to give. I want to thank you all for your contributions to this discussion. On behalf of our panel, we want to thank you for joining us and we hope you found this OncLive® Peer Exchange® discussion to be useful and informative.

Transcript Edited for Clarity 

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Transcript: 

Mark R. Litzow, MD: I want to thank each of you. This has been extremely informative. I appreciate your expert perspectives. I’d like to close by asking each of you to make some closing remarks. What excites you now in the field of ALL? What do you think the interesting questions are? Anthony, why don’t you start us off?

Anthony S. Stein, MD: Having taken care of ALL for the last 30 years, I think over the last 5 or 10 years, we have 3 exciting new promising agents: blinatumomab, inotuzumab, and CAR T cells. The question is going to be how to incorporate them as single agents together with chemotherapy or how to move them up into the up-front setting, where we already have a SWOG study for patients over the age of 65 with Ph-negative ALL who are only being treated with blinatumomab for 5 cycles and then going on a maintenance therapy. So, I think the results of that study will give us a lot of information about what the results of using immunotherapy are in an up-front setting. And then, we have the ECOG study randomizing patients to blinatumomab or consolidation chemotherapy. I think the goal in 5 to 10 years is hopefully to have a chemotherapy-free treatment for ALL so patients are not suffering from cardiac toxicity or neuropathy or needing treatment for 3 years at a time.

Mark R. Litzow, MD: Thank you. Aaron?

Aaron C. Logan, MD, PhD: I’m excited about a lot of things in the ALL space, one of which is the increasing awareness about measurable residual disease and ease of access to testing for it. I think every ALL patient, regardless of their age, needs to have MRD testing throughout the course of their therapy, because it can guide meaningful decisions about how to prevent that patient from relapsing and get them onto the right track. The accessibility of things like centralized labs for flow cytometry or next-generation sequencing are very, very important to enable that.

I’m excited about all of these new agents, not only because we can capture some of our relapsed/refractory patients for whom chemotherapy didn’t work but also because of this prospect that maybe we can achieve that goal of chemotherapy-free induction maintenance and consolidation and maybe eliminate transplant for even some of the high-risk patients. One of the things I find very difficult when taking care of a patient with ALL is when my adult patient says, “When can I return to work?” You’re thinking, “Well, if you do well and you stay on therapy, you’re going to be on chemotherapy for an awfully long time. And if you get a transplant, you’re going to be out of commission for an awfully long time.” I would love to get to a point where we can cure patients in the course of months and give them their lives back—let them return to work, let them return to their families—and that’s when I think we’re going to be having big impacts.

Mark R. Litzow, MD: Thank you. Ryan?

Ryan D. Cassaday, MD: Certainly, there’s a lot of excitement and optimism about the new agents and the potential power that they have. I think for me, as we get better at risk stratifying patients—both in terms of their baseline biologic features, whether it’s Ph-like or it’s RAS mutations in T-cell ALL—we’re still relying on some of those old school modalities, the cytogenetics and things like that. But then, there are better response assessments with better MRD techniques so that we can better tailor and understand who are those patients who are going to do well with the things we have now. Who do we really need to think about treating in an alternative manner, whether it’s with blinatumomab, intensified chemotherapy, transplant, or no transplant? Some of those goals I think are a little bit more in reach and something that we can get a handle on, even in the next year or two while we’re waiting for some of these bigger studies to come along and show that we can get rid of a lot of the chemotherapy and use some of these new agents.

Bijal D. Shah, MD: I think what we’re all saying is that we’re excited that we get to personalize therapy for our patients based on their biology, based on their response. We get to personalize it with nonchemotherapeutic options that have a potential to very meaningfully impact their survival. So, without a question, that’s what I’m excited about.

Mark R. Litzow, MD: Thank you. I would echo those thoughts. I think we can’t forget T-cell disease, which is still really a boondoggle around our necks, and we’re hoping that there will be further breakthroughs in that area. I think that using pediatric intensive regimens and using measurable residual disease and using immunotherapy have great potential to move us away from the amount of chemotherapy that we have to give. I want to thank you all for your contributions to this discussion. On behalf of our panel, we want to thank you for joining us and we hope you found this OncLive® Peer Exchange® discussion to be useful and informative.

Transcript Edited for Clarity 
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