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Acute Lymphoblastic Leukemia: Risk Stratification

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, Jan 29, 2018



Transcript: 

Mark R. Litzow, MD: Hello, and thank you for joining this OncLive® Peer Exchange® titled “Acute Lymphocytic Leukemia: Practical Perspectives.” Significant advances have been made in improving outcomes for patients with acute lymphoblastic leukemia, particularly with the availability of novel therapies such as blinatumomab, inotuzumab ozogamicin, and newer BCR-ABL tyrosine kinase inhibitors. More recently, we have seen the game-changing FDA approval of the first CAR T-cell therapy for younger patients with relapsed disease. However, for older patients with ALL, survival is still poor and there’s a need for less intensive but effective treatment strategies. In this OncLive® Peer Exchange® discussion, I am joined by a panel of experts in treating adult patients with ALL. Together we will discuss practical strategies for treatment and how to incorporate novel therapies into clinical practice.

I’m Dr. Mark Litzow, and I’m a professor of medicine, chair of the Leukemia Committee of ECOG -ACRIN, and head of the Acute Leukemia Group at the Mayo Clinic in Rochester, Minnesota. Participating today on our distinguished panel are Dr. Ryan Cassady, assistant professor in the Division of Hematology at the University of Washington School of Medicine in Seattle, Washington; Dr. Aaron Logan, assistant professor of hematology and bone marrow transplant at the University of California San Francisco in San Francisco, California; Dr. Bijal Shah, assistant member of the Department of Malignant Hematology at the Moffett Cancer Center in Tampa, Florida; and Dr. Anthony Stein, clinical professor at the Gehr Family Center for Leukemia Research, City of Hope, in Duarte, California. Thank you so much for joining us. Let’s begin.

Our first segment is on induction therapy for adult acute lymphoblastic leukemia. Before we talk about therapy, we need to talk about the initial assessment of patients when they’re first diagnosed and how we classify and prognosticate about the patients. Ryan, can I ask you to elaborate on some of the features of how we assess patients at diagnosis?

Ryan D. Cassaday, MD: There’s certainly a lot of heterogeneity and complexity when managing adults with ALL. Age is a common criterion that we use. At least in my practice, and I think in many others, we define young adults with ALL depending on the specific study used. It might vary a bit, but generally speaking, if you’re talking about someone the age of 40, that would be considered a young adult. When you start to get over the age of 60 or so, then you start to talk about elderly patients. The way that we manage that across the spectrum can really vary depending on goals of therapy, their ability to tolerate certain regimens, and so forth. Along with that comes changes in the biology of the disease. Generally speaking, older patients are more likely to have adverse biologic factors in their disease, whether it’s cytogenetic abnormalities or the like.

As for other risk classification systems that we use historically, high white blood cell count is something that has stood the test of time as an adverse prognostic factor. As we’ve established a little bit more of an understanding about the biology of the disease though, cytogenetic abnormalities like MLL rearrangements, complex karyotypes, the Philadelphia chromosome’s presence or absence, these are the things that we look at a lot in terms of understanding those baseline characteristics that can help us understand how to treat patients.

Mark R. Litzow, MD: Bijal, what’s your perspective on this? In particular, could you comment about some of the molecular assessments and this newer category of Ph-like ALL?

Bijal D. Shah, MD: Absolutely. I think what we’re seeing more and more, particularly in our young adult population, is a high frequency of Ph-like abnormalities, which we define as rearrangements of CRLF2 and JAK2 predominantly. There are other rearrangements involving PDGFR and other kinase pathways, but really CRLF2 and JAK2 stand out. They’re going to account for the overwhelming majority of Ph-like patients who we’ll see. I do think it’s important to identify these patients up front. I think these patients are more likely to have MRD at the end of therapy and are more likely to fail therapy. And so, understanding that dynamic gives us the opportunity to start thinking from day one, how are we best going to optimize our sequence of therapies if indeed we need to sequence multiple therapies to achieve the best outcome for these patients?

Transcript Edited for Clarity 

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Transcript: 

Mark R. Litzow, MD: Hello, and thank you for joining this OncLive® Peer Exchange® titled “Acute Lymphocytic Leukemia: Practical Perspectives.” Significant advances have been made in improving outcomes for patients with acute lymphoblastic leukemia, particularly with the availability of novel therapies such as blinatumomab, inotuzumab ozogamicin, and newer BCR-ABL tyrosine kinase inhibitors. More recently, we have seen the game-changing FDA approval of the first CAR T-cell therapy for younger patients with relapsed disease. However, for older patients with ALL, survival is still poor and there’s a need for less intensive but effective treatment strategies. In this OncLive® Peer Exchange® discussion, I am joined by a panel of experts in treating adult patients with ALL. Together we will discuss practical strategies for treatment and how to incorporate novel therapies into clinical practice.

I’m Dr. Mark Litzow, and I’m a professor of medicine, chair of the Leukemia Committee of ECOG -ACRIN, and head of the Acute Leukemia Group at the Mayo Clinic in Rochester, Minnesota. Participating today on our distinguished panel are Dr. Ryan Cassady, assistant professor in the Division of Hematology at the University of Washington School of Medicine in Seattle, Washington; Dr. Aaron Logan, assistant professor of hematology and bone marrow transplant at the University of California San Francisco in San Francisco, California; Dr. Bijal Shah, assistant member of the Department of Malignant Hematology at the Moffett Cancer Center in Tampa, Florida; and Dr. Anthony Stein, clinical professor at the Gehr Family Center for Leukemia Research, City of Hope, in Duarte, California. Thank you so much for joining us. Let’s begin.

Our first segment is on induction therapy for adult acute lymphoblastic leukemia. Before we talk about therapy, we need to talk about the initial assessment of patients when they’re first diagnosed and how we classify and prognosticate about the patients. Ryan, can I ask you to elaborate on some of the features of how we assess patients at diagnosis?

Ryan D. Cassaday, MD: There’s certainly a lot of heterogeneity and complexity when managing adults with ALL. Age is a common criterion that we use. At least in my practice, and I think in many others, we define young adults with ALL depending on the specific study used. It might vary a bit, but generally speaking, if you’re talking about someone the age of 40, that would be considered a young adult. When you start to get over the age of 60 or so, then you start to talk about elderly patients. The way that we manage that across the spectrum can really vary depending on goals of therapy, their ability to tolerate certain regimens, and so forth. Along with that comes changes in the biology of the disease. Generally speaking, older patients are more likely to have adverse biologic factors in their disease, whether it’s cytogenetic abnormalities or the like.

As for other risk classification systems that we use historically, high white blood cell count is something that has stood the test of time as an adverse prognostic factor. As we’ve established a little bit more of an understanding about the biology of the disease though, cytogenetic abnormalities like MLL rearrangements, complex karyotypes, the Philadelphia chromosome’s presence or absence, these are the things that we look at a lot in terms of understanding those baseline characteristics that can help us understand how to treat patients.

Mark R. Litzow, MD: Bijal, what’s your perspective on this? In particular, could you comment about some of the molecular assessments and this newer category of Ph-like ALL?

Bijal D. Shah, MD: Absolutely. I think what we’re seeing more and more, particularly in our young adult population, is a high frequency of Ph-like abnormalities, which we define as rearrangements of CRLF2 and JAK2 predominantly. There are other rearrangements involving PDGFR and other kinase pathways, but really CRLF2 and JAK2 stand out. They’re going to account for the overwhelming majority of Ph-like patients who we’ll see. I do think it’s important to identify these patients up front. I think these patients are more likely to have MRD at the end of therapy and are more likely to fail therapy. And so, understanding that dynamic gives us the opportunity to start thinking from day one, how are we best going to optimize our sequence of therapies if indeed we need to sequence multiple therapies to achieve the best outcome for these patients?

Transcript Edited for Clarity 
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