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How Will I Know if My AML Treatment is Working?

How Will I Know if My AML Treatment is Working? from Patient Empowerment Network on Vimeo.

During acute myeloid leukemia (AML) treatment, specific tests help to gauge a patient’s treatment response. Dr. Pinkal Desai details how diagnostic tests are used in monitoring the efficacy of an AML therapy

Dr. Pinkal Desai is Assistant Professor of Medicine at Weill Cornell Medical College and a hematologist specializing in acute myeloid leukemia (AML) at Weill Cornell Medicine. Learn more about Dr. Desai, here.

Download Program Resource Guide

See More From The Pro-Active AML Patient Toolki

Related Resources:

What Are the Goals of AML Treatment?

What Are the Goals of AML Treatment?

Choosing an AML Treatment Path: What Should You Consider?

Choosing an AML Treatment Path: What Should You Consider?

What Is the Patient’s Role in Making AML Treatment Decisions?

What Is the Patient’s Role in Making AML Treatment Decisions?

Transcript:

Katherine:                  

Once a patient has started treatment, how do you know if it’s working? How do you gauge that?

Dr. Desai:                   

When a patient begins treatment, whatever their regimen is, for the most part, it takes about a month to get into remission. So, initially, with any treatment we would use, the blood counts will actually go down. Everything is down, down, down. That’s important, and it’s good, actually, because if we can’t wipe out these cells, then we’re not going to. The patient’s not going to go into remission. It’s good that these blood counts drop and they keep like that for a month.

After a month, generally, is the first look on an average to see where it is, and that kind of depends on the regimen. For intensive chemotherapy, we take a look in the middle, like Day 14, to see did we wipe out all the leukemia? And can we modify treatment so that whatever might be left behind will clean out? For lower intensity treatments, it’s about a month. So, that’s the first sort of real look at whether a patient is in remission.

And again, when I say, remission is a morphologic criteria that we see the blast count are less than 5 percent, and the cells are – the normal cells are back to what is considered within normal limits or normal for that person’s age. And the idea, at that time, is to not only just confirm remission, but like I was saying, how good is the remission.

So, that’s where MRD testing comes into play. You want to see what you want to find, even if it’s by small numbers, what is the percentage of leukemia that’s left behind. 0.01 percent, 0.001 percent. This is important.

The goal is to ultimately get that down to zero, and that’s how we use it during induction, even when they’re going through consolidation, we’re episodically monitoring with bone marrow or blood testing for some of these molecular mutations that is there continued response from where we started off? And once the treatment is done, we are still, we’re seeing these patients on a regular basis, sometimes doing bone marrow biopsies at regular intervals, to again make sure that there is continued response. And can we see something different, or is there an emerging population of cells that are worrisome, and how do we modify our treatments to try to kill these cells?

What Could Emerging AML Treatment Approaches Mean for You?

What Could Emerging AML Treatment Approaches Mean for You? from Patient Empowerment Network on Vimeo.

In the changing landscape of acute myeloid leukemia (AML) research, how could emerging treatments impact care for patients? Dr. Pinkal Desai shares information about combination therapies, immunotherapy, and clinical trials, and explains the value of MRD in tracking AML response.

Dr. Pinkal Desai is Assistant Professor of Medicine at Weill Cornell Medical College and a hematologist specializing in acute myeloid leukemia (AML) at Weill Cornell Medicine. Learn more about Dr. Desai, here.

Download Program Resource Guide

See More From The Pro-Active AML Patient Toolki

Related Resources:

What Are the Goals of AML Treatment?

What Are the Goals of AML Treatment?

Choosing an AML Treatment Path: What Should You Consider?

Choosing an AML Treatment Path: What Should You Consider?

AML Treatment Decisions: What’s Right for You Resource Guide

Transcript:

Katherine:                  

Are there emerging approaches for treating AML that patients should know about?

Dr. Desai:                   

So, there are several, and this is where there’s lots of lots of new drugs that have been approved. A lot of drugs in the pipeline. And within the categories, you can divide up where the advances are being made in several categories. So, the first one is, can you make a better induction regimen? So, how can you combine chemotherapy or hypomethylating agent plus venetoclax combination?

Can you add more targeted agents to these bad points to improve the chances of remission and to keep the patients in remission? So, that’s one aspect of it, that this is important.

There’s obviously this whole concept of immunotherapy of AML, where there’s a lot of antibodies treatment or drugs that affect the immune modulation that are being used both in up-front leukemia, in many times in the older patients, itself. There are clinical trials, obviously.

And also, in the relapse setting, there are CAR-T cells being used in leukemia therapy in the relapse setting. This is important, and a lot of new drugs are being used in the relapse setting. So, there’s this whole new sort of portfolio of clinical trials and treatment options for patients.

And the third aspect, which is, I would say, very important and as important as using better drugs, is to be able to quantify how the patients are responding to these treatments. Because we don’t want to start treatment, and then be blind about the kind of responses they’re getting.

There’s a whole new concept, what we call MRD measurements, or minimal residual disease, or measurable residual disease, MRD monitoring. That’s very important. So, when a patient starts with chemotherapy, and then you have subsequent bone marrows, even if they’re in remission, the quality of remission matters. The amount of MRD or amount of leukemia that’s left behind matters. And how do we direct our treatments to clean up that MRD? And how do we monitor this MRD, so that we can see what happens in the future? Many times, MRD can tell us that a patient’s going to relapse six months later. And how do we use that information?

So, these are very important aspects of monitoring of treatment that is important, and to measure MRD, not just by looking at the cells themselves, but using the patient’s own signature of molecular mutations that we found at baseline at the time of diagnosis. And how do we keep an eye on that?

This is another new world and new ways to figure out how best to use new drugs, maintenance approaches, better consolidation approaches, and how do we use MRD to mix all of these together to get the best possible outcome for these patients.

I think we’ve seen tremendous progress in leukemia, just over the last five years. We went from pretty much having two drugs to treat leukemia, chemotherapy, 7 and 3, and some hypomethylating agents, to a flurry of 15 new approvals. We now have targeted therapies. We have new clinical trials. I’m very hopeful that the combination of all of the things that we’re talking about, how to monitor patients, how to best utilize stem cell transplants. We’re entering a new age in leukemia, and I’m hopeful that with the advent of all of these drugs and what we know about leukemia, we can actually have a very good shot now to improve cure rates in leukemia.

AML Treatment Approaches: What You Should Know About Your Options

AML Treatment Approaches: What You Should Know About Your Options from Patient Empowerment Network on Vimeo.

What should acute myeloid leukemia (AML) patients and care partners know about treatment options? Dr. Pinkal Desai shares information about frontline treatments, targeted therapies, combination therapies, and clinical trials, and explains an important clarification regarding a newly approved oral hypomethylating agent.

Dr. Pinkal Desai is Assistant Professor of Medicine at Weill Cornell Medical College and a hematologist specializing in acute myeloid leukemia (AML) at Weill Cornell Medicine. Learn more about Dr. Desai, here.

Download Program Resource Guide

See More From The Pro-Active AML Patient Toolki

Related Resources:

What Are the Goals of AML Treatment?

What Are the Goals of AML Treatment?

Choosing an AML Treatment Path: What Should You Consider?

Choosing an AML Treatment Path: What Should You Consider?

Understanding Risk in AML: How Molecular Testing Affects Treatment Option

Transcript:

Katherine:                  

So, in looking at a treatment plan, we’ve discussed the factors that go into that choice. And then, you’ve also just covered some treatment approaches and who they might be right for. So, you’ve talked about chemotherapy. You’ve talked about stem cell transplant. What about targeted therapies and also clinical trials? Where do they fit in?

Dr. Desai:                   

Right now, if somebody’s diagnosed with new AML or newly diagnosed leukemia, and they are eligible for intensive chemotherapy of the approved agents, the one targeted therapy that does make a difference is midostaurin, which is a FLT3 inhibitor.

And patients who do have a FLT3 mutated leukemia, the standard of care is treatment with intensive chemotherapy in combination with midostaurin. So, this is where chemotherapy’s combined with the backbone of the targeted therapy.

There are clinical trials of other targeted therapies that are being combined with frontline treatment. That frontline treatment might be intensive chemotherapy or more of the hypomethylating-based therapy, which is what we call lower intensity therapy. So, these are where the clinical trials are asking the question that can be just how midostaurin was combined with chemotherapy.

Can we combine other targeted therapies with the backbones that currently exist? Chemotherapy or lower intensity hypomethylating agents. And can we combine them to improve the chances of going into remission and staying in remission?

I would say clinical trials are extremely important. Almost any stage of leukemia, whether it’s a new diagnosis, whether it’s second-line or relapse, it’s important, because these questions that are being asked are very relevant. How do we improve upon the existing known remission rates and survival in leukemia?

There are targeted therapies available for IDH inhibitors that are being combined. There is also a newly approved BCL2 inhibitor, venetoclax, which is used in combination with hypomethylating agents, that have shown survival advantage over single agent.

Hypomethylating agents, anybody who’s older, we are now combining the venetoclax with hypomethylating agents for what we call lower intensity induction treatment. And there are several others in the making. We have TP53 inhibitors.

As we talked about this, that leukemia is not one diagnosis, really. AML has several, several, several subtypes, and once we find out what makes that particular patient’s leukemia tick, and if you have a targeted inhibitor towards it, it’s logical that you would want to combine it with what the backbone of treatment is, and that’s where clinical trials are extremely important in asking most relevant questions and improving patient survival. 

Katherine:

Dr. Desai, I learned that oral azacitidine was recently FDA approved. What does that approval mean for patients and who is it right for?

Dr. Desai:                   

So, oral… So, azacitidine. For patients who may or may not know this, azacitidine has been approved in the IV or subcutaneous formulation for treatment of myelodysplastic syndrome and leukemia.

And this is, when I was saying that there is a lower intensity treatment of hypomethylating agents, that’s one of the drugs, azacitidine. And we use it for induction treatment in patients who do not qualify for intensive chemotherapy in AML.

So, oral azacitidine has been currently approved for older patients who have gone through intensive chemotherapy.

The trial was done in patients who did not have prior hypomethylating exposure of any kind, so people who had not seen any IV or subcutaneous azacitidine, they had leukemia, they get the intensive chemotherapy, finish the induction part, and the, what we call, consolidation part, which is the cleaning up with more additional cycles of chemotherapy.

Once that is done, the old standard of care was to not do anything, so these are obviously for patients who are not transplanted. So, once somebody, just to give a background on this, if somebody’s in remission and they’re transplant eligible, we make a decision whether they should go for transplant or they should get some more chemotherapy rounds. Both are consolidation of some kind, transplant or chemotherapy.

So, let’s say somebody went through induction, got into remission, and it was decided that they’re not candidates for transplant, or the patient didn’t want to go through a transplant, and you go for the consolidation. And the old standard was, after that, to do nothing. And oral azacitidine was tested in this situation, where half the patients got oral azacitidine as maintenance. It was given as pills, to take it for two weeks out of a 28-day cycle.

So, every month, you take it for 14 days. And half of them didn’t get the drug, oral azacitidine. And the drug was recently approved for FDA for having a survival advantage over the standard of care, which is to do nothing after consolidation is over.

So, in other words, this is currently available for patients, older patients, who’ve gone through induction chemotherapy, and/or consolidation, and then finished it. Then, you start this oral azacitidine for keeping this remission going on longer. And that’s where the niche of this drug is.

It is very, very important to understand that oral azacitidine has a very different kinetic in the body than IV azacitidine. So, I think people, many times, get confused between is IV the same as oral? They are totally different drugs and have a different way it affects the bone marrow.

So, they’re not to be interchanged for that indication. Oral azacitidine has been strictly approved for maintenance of remission, post-chemotherapy.

What Is the Patient’s Role in Making AML Treatment Decisions?

What Is the Patient’s Role in Making AML Treatment Decisions? from Patient Empowerment Network on Vimeo.

What role do acute myeloid leukemia (AML) patients have in their treatment decisions? Dr. Pinkal Desai explains factors that go into decision-making and how patients may help guide the treatment option that’s best for them.

Dr. Pinkal Desai is Assistant Professor of Medicine at Weill Cornell Medical College and a hematologist specializing in acute myeloid leukemia (AML) at Weill Cornell Medicine. Learn more about Dr. Desai, here.

Download Program Resource Guide

See More From The Pro-Active AML Patient Toolki

Related Resources:

What Are the Goals of AML Treatment?

What Are the Goals of AML Treatment?

Choosing an AML Treatment Path: What Should You Consider?

Choosing an AML Treatment Path: What Should You Consider?

Being Pro-Active in Your Care: Key AML Testing to Advocate For

Transcript:

Katherine:                  

What is the patient’s role in this decision?

Dr. Desai:                   

I think it’s important for patients to understand why the decisions are being made or what goes into the decision-making. Because the patients would appreciate, if they know, that these are the genetic subtypes, and this would be the best sort of approach for them.

So, from a patient’s side, their role is, 1) to understand all the factors that go into the decision-making. And the second aspect, which is important, is their own values and their own decision on what treatment they would like to have. 

So, there are – sometimes, it’s very white and black. There are many times where it’s a gray zone, in the sense that there is a best treatment that’s available, that the oncologist would discuss, but it’s also possible to choose between two different kinds of therapy options.

If the patient is eligible, for example, for both intensive and non-intensive treatment, then what would they prefer based on what’s going on in their life? Whether they want to be hospitalized for 30 days for intensive induction or not? Do they want to do this out-patient? A lot of these things are important, and they have to be involved with this.

The third aspect, which is very important from a patient standpoint, is the need for transplant. So, patients who are younger and transplant eligible for leukemia that has a higher risk of coming back, we do recommend a stem cell transplant, so that the patients have to understand the process of stem cell transplant.

Sometimes, it’s slam dunk that a transplant is needed, but there are certain times where you could or could not go for it, and this is where the patient’s choices and values are extremely important, that once they hear all of this information, they would decide whether they should or should not go for stem cell transplant.

Choosing an AML Treatment Path: What Should You Consider?

Choosing an AML Treatment Path: What Should You Consider? from Patient Empowerment Network on Vimeo.

What should be considered when choosing an acute myeloid leukemia (AML) treatment path? Dr. Pinkal Desai explains the factors that are considered to determine the best treatment for an individual patient.

Dr. Pinkal Desai is Assistant Professor of Medicine at Weill Cornell Medical College and a hematologist specializing in acute myeloid leukemia (AML) at Weill Cornell Medicine. Learn more about Dr. Desai, here.

Download Program Resource Guide

See More From The Pro-Active AML Patient Toolki

Related Resources:

What Are the Goals of AML Treatment?

What Are the Goals of AML Treatment?

Effective AML Combination Treatment

AML Treatment Decisions: What’s Right for You Resource Guide

Transcript:

Dr. Desai: 

Now, in terms of how we decide treatment, so, there is the leukemia aspect of it, of the biologic indicators of leukemia, and there’s obviously the patient. Because everybody is different. There are patients who are coming in at various ages, like you said. Age is a very important thing to look at, because if you’re younger, the patient’s younger, then they’re usually eligible for what we call intensive chemotherapy. And if the patient is older, they may not be able to handle intensive chemotherapy, and in which case, the induction treatment or the first treatment, we call induction treatment, is basically the treatment we give to get you into remission.

So, the induction treatment decision is based largely from a patient aspect on age.

Whether to go with intensive induction chemotherapy, or with lower intensive chemotherapy, depending on the person’s age.

Now, age is… There is a loose definition of what is considered older age, but we generally say over 75, patients cannot handle intensive chemotherapy. Under 75, under 70 for sure, they’re eligible for intensive chemotherapy, but it’s a biological continuum. So, there are patients who are much healthier, even at older ages, and much older at younger ages. So, we take into consideration not just the age, but also what else do they suffer from? Do they have other comorbidities? Is the heart okay? Do they have kidney damage? Do they have lung damage from previous comorbid illness? And that all goes into figuring out what kind of treatments can they handle.

And that’s the patient aspect of it. Then there’s the biologic aspect of the leukemia itself. Leukemia, the chromosome type. There are leukemias that respond extremely well to intensive chemotherapy. So, you’d figure that kind of treatment for it. Within the molecular subclassification, as we said, there are mutations in certain genes, like FLT3 and IDH. There are targeted treatments towards that, so we look at all of these genes to figure out what is the best mix of chemotherapy, targeted therapy, lower intensity therapy, to look at and combine so that we can have the best chance of being in remission, and to continue to be in remission.

What Are the Goals of AML Treatment?

What Are the Goals of AML Treatment? from Patient Empowerment Network on Vimeo.

When it comes to acute myeloid leukemia (AML), what are the goals of treatment? Dr. Pinkal Desai defines the role of remission and the specific goals of treatment for AML patients. 

Dr. Pinkal Desai is Assistant Professor of Medicine at Weill Cornell Medical College and a hematologist specializing in acute myeloid leukemia (AML) at Weill Cornell Medicine. Learn more about Dr. Desai, here.

Download Program Resource Guide

See More From The Pro-Active AML Patient Toolki

Related Resources:

How Is Acute Myeloid Leukemia Treated?

Being Pro-Active in Your Care: Key AML Testing to Advocate For

AML Treatment Decisions: What’s Right for You Resource Guide

Transcript:

Katherine:      

Dr. Desai, when deciding on a treatment approach with a patient, I imagine you have to consider a number of factors, like a patient’s age and their overall health. Let’s walk through these considerations, and we’ll start with treatment goals. What does that mean, exactly?

Dr. Desai:                   

So, the first treatment goal is to get into remission. Patients with leukemia will have abnormal blood counts, they don’t feel well, they have a risk of infection, and all of that is only going to get better if you can get into remission.

And remission means that the bone marrow has a blast count less than 5 percent. Now, remember, we talked about if it was over 20, it’s considered diagnosis of AML. So, we want it gone under 5 percent, preferably zero. And we want all the blood counts that are abnormal to normalize back to what it would be for a normal person.

So, that’s the sort of definition of remission, and we want to get there, because ultimately, patients feel extremely good once they go into remission. They feel fine. The risk of infection goes away. It is absolutely important for long-term quality of life and survival. The first goal is to get into remission.

The second goal is to keep that remission going, for as long as possible, and also increase the chances of cure.

So, going into remission does not mean that a patient is cured of leukemia. It means that we’ve taken the first step of knocking the leukemia down to its knees, but there are still a few cells that are hanging out, and they’re still hiding. And the rest of the treatment and approach is to try to kill these cells and improve the chances of cure. So, and generally we say, once you get into remission you stay in remission, and when you’re past that five-year mark, we say leukemia is cured.

So, the first goal is get into remission. Second, keep yourself in remission, and that’s the whole sort of few things that we look at.

Understanding Risk in AML: How Molecular Testing Affects Treatment Options

Understanding Risk in AML: How Molecular Testing Affects Treatment Options from Patient Empowerment Network on Vimeo.

How does molecular testing impact acute myeloid leukemia (AML) treatment options? Dr. Pinkal Desai discusses molecular testing and how results may help determine the best treatment path for patients.

Dr. Pinkal Desai is Assistant Professor of Medicine at Weill Cornell Medical College and a hematologist specializing in acute myeloid leukemia (AML) at Weill Cornell Medicine. Learn more about Dr. Desai, here.

Download Program Resource Guide

See More From INSIST! AML

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Genetic Mutations That Impact AML Prognosis and Treatment 

Should AML Molecular Testing Be Repeated?

Insist! AML Resource Guide

Transcript:

Katherine:      

Dr. Desai, is there a high-risk and a low-risk AML? And if so, what are the indicators?

Dr. Desai:                   

So, in terms of when we talk about risk of leukemia, many patients, when they come, they frequently ask what stage this is, which is generally not how leukemia is categorized, unlike lung cancer, or breast cancer, or any of the solid tumors. Leukemia is in your blood and in your bone marrow, so it’s kind of like all or none to some extent. When we talk about risk in leukemia, we’re talking about what is the chance of this leukemia coming back in the future. So, is the chance high, intermediate, or low?

And that’s how we categorize leukemia, into these three sort of risk categories, low risk, intermediate risk, and high risk. These risk categories are made up.

We decide these based on information from two aspects. One is the chromosomes, which we talked about. There are certain good risks of chromosomal abnormalities as well, where, for example, poor binding factor leukemias, where these leukemias tend to respond very well to chemotherapy. There are some higher risk, that the chances are higher to come back. And then, the middle category of intermediate risk, where it’s sort of in the middle.

The molecular subtype, or the molecular classification of AML is extremely, extremely relevant, because it gives you pretty much your own signature, and the patient sort of specific, personalized risk of whether this is going to have a high, intermediate, or a low risk to come back.

So, it’s a combination of chromosomes, and the molecular subtype, which is extremely important in figuring out the risk category.

Now, in the course of the treatment and decision-making of leukemia, we don’t have – we’ll have the chromosome information quite early, usually within the first two to three days, but the molecular information, some of it comes back pretty fast, like in a couple days from the testing. But many of these tests, the full panel comes back about 14 days after we do the original bone marrow biopsy. Some of these decisions on whether this is high risk or low risk is relevant in the long run. These decisions happen later, and you don’t have to wait for the treatment, obviously. This is more for what happens after a patient goes into remission.

But there are certain molecular genes that are very important in deciding treatment up front, and those we expedite, and they are back usually before treatment decision is made. For example, FLT3 ITD or FLT3 TKB.

These are two genes where the up-front treatment decision changes, depending on the presence or absence of this gene. So, you really, really do want to know this information early on.

Chromosomes you absolutely need it before treatment begins, because there are several options of leukemia treatment that are specific to certain chromosome subtypes. So, that’s like the basic information you need to have before making any treatment plans.

Key AML Testing for Better Care: Understanding Prognosis and Treatment Choices

Key AML Testing for Better Care: Understanding Prognosis and Treatment Choices from Patient Empowerment Network on Vimeo.

After an acute myeloid leukemia (AML) diagnosis, additional tests must follow to determine prognosis and treatment options. Dr. Pinkal Desai explains key tests that aid in choosing optimal care for each patient. 

Dr. Pinkal Desai is Assistant Professor of Medicine at Weill Cornell Medical College and a hematologist specializing in acute myeloid leukemia (AML) at Weill Cornell Medicine. Learn more about Dr. Desai, here.

Download Program Resource Guide

See More From INSIST! AML

Related Resources:

Being Pro-Active in Your Care: Key AML Testing to Advocate For 

Should AML Molecular Testing Be Repeated?

Confused About AML Genetic Testing and Treatment? What You Need to Know

Transcript:

Katherine:      

Other than a complete blood count, what additional testing should take place following an AML diagnosis?

Dr. Desai:                

So, a blood count or CBC is just a hint that there might be AML. It’s certainly not diagnostic.

But when you see that there are some abnormalities in blood count, and there might be the presence of these immature cells or blasts in circulation, there is suspicion that this is acute myeloid leukemia. The diagnosis, the gold standard for diagnosis, is a bone marrow biopsy, which is a procedure that can be done out-patient or in the hospital, depending on where the patient is. It takes about 15 minutes, where we take a sample out of the hip bone and look at the cells. This is where bone marrow is being made, so you’re going to exactly where the problem lies, and seeing if the blast count is increased.

So, the diagnosis of AML is established when the blast count is over 20 percent in the bone marrows. And normally, it needs to be less than 5 percent.

And if it’s over 20 percent, that’s the diagnosis of AML. Whether it’s over 20 percent in the bone marrow or in the peripheral blood.

It doesn’t matter, one way or the other. This is a diagnosis of AML, but you do need a bone marrow biopsy to confirm diagnosis of AML.

Katherine:                  

What about genetic or molecular testing? Is that done?

Dr. Desai:                   

AML diagnosis is just one part or the first step of saying somebody has leukemia. There is a slew of other tests that are important, and we generally consider, within the genetic tests, we generally consider two kinds of testing. One is the cytogenetics, or the karyotype analysis, which looks at the chromosomes in our bodies.

So, leukemia can be associated with big chromosomal changes, and that’s important to recognize. And the second one is the molecular testing, and we’ll go over both of them.

The chromosomes, or the karyotypic analysis, the vast majority of leukemia patients have a normal chromosome type, but there are certain recurrent abnormalities in chromosomes that we see in leukemia, and that’s important to know for a variety of reasons: treatment decisions, prognostication.

And the second part of it, the molecular, these are actually genetic routine analysis, and this is not somebody – it doesn’t mean, when we say genetic testing, it’s not the patient’s own normal genetic type. So, we’re not looking for what they have inherited. Most of leukemia is actually a random event, and it’s not inherited. We’re talking about genetic damage that the leukemia cells have within themselves.

It gives us the signature of the leukemia, and it helps us understand what genetic abnormalities are present in the leukemia. There are several panels, 50 to 100 genes, but there’s usually recurrent genetic damage that leukemia cells have.

And you want to know that, because again, like karyotype, this is important in treatment decisions, and also in the prognostication and prediction in the future.

Treatment Approaches in AML: Key Testing for Personalized Care

Treatment Approaches in AML: Key Testing for Personalized Care from Patient Empowerment Network on Vimeo.

When it comes to Acute Myeloid Leukemia (AML), genetic testing (or biomarker testing) is essential in helping to determine the best treatment approach for YOU. In this program, AML expert, Dr. Naval Daver reviews key decision-making factors, current AML treatments and emerging research for patients with AML.

Dr. Naval Daver is an Associate Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. More about Dr. Daver here.

Download Program Resource Guide

See More From INSIST! AML

Related Resources:

 

How is Acute Myeloid Leukemia (AML) Treated?

 

Effective AML Combination Treatment: Pairing Old and New Therapies

 

Confused About AML Genetic Testing and Treatment? What You Need to Know

Transcript:

Katherine:                   

Welcome to INSIST! AML. A program focused on empowering patients to insist on better care. Today we’ll discuss the latest advances in AML, including the role of genetic testing and how this may affect treatment options. I’m Katherine Banwell, your host for today’s program. And joining me is Dr. Naval Daver. Welcome, Dr. Daver. Thank you so much for being here. Would you introduce yourself?

Dr. Daver:                    

Hello. Yeah. Thank you very much, Katherine. It’s a pleasure to join this discussion and meeting. I’m the Associate Professor in the Department of Leukemia at the MD Anderson Cancer Center. I focus on the treatment of acute myeloid leukemia and MDS, including the development of a number of clinical trials that are using targeted therapies and immune therapies for this disease. And with the great and dramatic progress, we’re seeing in acute myeloid leukemia; I think it is now more important than ever for patients to be aware of the options and be able to select the most appropriate therapy with their physicians.

Katherine:                   

Before we get into the discussion about AML, a reminder that this program is not a substitute for seeking medical advice. Please refer to your own healthcare team. Dr. Daver, I know the field of AML research is advancing rapidly. Would you give us an overview of the current treatment types in AML?

Dr. Daver:                    

There has been dramatic progress in the treatment of acute myeloid leukemia, especially in the last three years. We’ve had eight new drugs approved for the treatment of acute myeloid leukemia. The most progress I think that has happened so far is in the identification of particular molecular mutations and targeting those mutations with targeted therapies.

The mutations that are most important right now and have target options for FLT3 mutations, F-L-T-3, and the drugs that have been USDA-approved for this are an agent called Midostaurin, which is a first-generation FLT3 inhibitor and combination chemotherapy.

And then, more recently, another agent called Gilteritinib, as a single agent in relapse refractory FLT3 AML. The other mutational group that is also very important, and therapeutically needs to be checked, is IDHN1 and IDH2. And there are now two IDH inhibitors, IDH1 inhibitor, Ivosidenib, and IDH2 inhibitor, Enasidenib, both of which have been approved by the United States FDA for relapse patients with IDH1, IDH2 mutations. So, I think it’s really critical now to check for particular molecular mutations and to appropriately add the particular targeted therapy or select the particular targeted therapy in patients who have the mutation.

The other major area of advancement, and probably, if not the most important breakthrough that has happened, is the development of a new drug called Venetoclax. This is a BCL2 inhibitor. It’s new in AML, but in fact, it has been used for many years in CLL, which is chronic lymphocytic leukemia.

And this drug, in combination with Azacitidine in the frontline setting in older patients with AML who are not good candidates for intensive induction, has shown very high response rates, almost 70 percent CR-CRi, which is more than double of the 20 to 25 percent we were getting with Azacitidine alone.

And it’s now been approved by the US FDA and, in my opinion, and many of the experts really is the new standard of care and should be used in all older patients who are not good candidates for intensive chemotherapy given both the very high response rates, as well as now mature data showing significantly improved overall survival and a good tolerability.

So, there are many other breakthroughs. But I think these targeted agents, and Venetoclax, probably are the most impactful today.

And we’re focusing a number of new combinations building around this.  

Katherine:                   

What are common mutations in AML?

Dr. Daver:                    

Yeah. So, the most common mutation in AML is F-L-T-3, FLT3 mutation. This is both prognostically important mutation, presence of an FLT3 in a newly diagnosed AML, has been shown in many large publications by the German Cooperative Group, British Cooperative Group, our group, and others, is associated with an inferior survival.

Also, now, on top of that, it is also a therapeutically important mutation in addition to having negative prognostic value because the addition of FLT3 inhibitors seems to dilute, to a large extent, the negative prognostic value.

So, we believe that if we can identify FLT3 mutations at FLT3 inhibitors, we can definitely improve the outcome of those patients. The second most common is what we call NPM1 mutation, and that tends to occur with FLT3. About 55 percent of patients with an FLT3 mutation will have a coopering NPM1.

NPM1 is very interesting. With NPM1 mutation is present on it’s own without a FLT3, it’s actually associated with favorable outcome. It’s a favorable prognostic marker. However, if NPM1 is present with a FLT3, and especially if the FLT3 has a high quantity, high allelic load, then the NPM1 loses its favorable impact. So, now we’re kind of moving beyond just; do you have one mutation or not, which is what we thought 10 years ago, to; well, yes, you have this mutation, but what about the core-occurring mutation and even beyond. What about the burden, or what we call the variant allele frequency of that mutation?

So, for good or bad and I think it’s good in the end because it’s going to improve the patient outcomes, that we are getting more, more in-depth and there’s no longer quote, unquote, AML.

So, there’s a lot more granularity and analysis that is required even before starting treatment. And this is the thing that, in the community, we’re educating the doctors a lot, is that it’s okay to wait four to six days, especially if the patient does not have a very proliferative leukemia, to get the important bloodwork to identify the appropriate molecular and chromosome group.

So, that we can select the right treatment which will improve outcome rather than just rushing into standard treatment and missing a particular molecular chromosome group.

Katherine:                   

True. It might not be – the genetic testing might not be right for everyone.

Dr. Daver:                    

Right. Right.

Katherine:                   

What is genetic testing in AML?

Dr. Daver:                    

So, genetic testing in AML is basically what we call molecular profiling.

So, it’s looking at the presence of particular molecular mutations. For example, at MD Anderson, we do what we call 81 gene panel. So, this looks at 81 different genes for mutations in the bone marrow of newly diagnosed acute myeloid leukemia. Now, how did we come up with 81 genes? So, this was actually done by literature analysis and review of previously published preclinical and translational studies, and we basically selected all mutations that had been shown to occur in two percent or more of thousands of AML patients. And we found 81 such mutations. So, that any mutation that had a two percent or higher frequency in known published or public databases was included.

And that’s how we’re able to analyze for the mutation. So, it’s still possible that there may be some very rare mutations that are present, and those may be important for research. But they don’t change our treatment decision today. And so that’s what we call genetic profiling. Some people call it molecular mutation analysis. Some people call it next-generation sequencing.

But basically, this is looking for mutations in particular genes that are known to occur in AML. Now of those 81 genes; and some people do a 100 gene panel, some do 50, so those are variables; but among those, there are four or five that are most important: the FLT3, as we discussed, where we can use FLT3 inhibitors; IDH1 and two, because we can use IDH1 and IDH2 inhibitors; TP53 is a very important mutation because it has very high risk and adverse prognosis.

And there are now new drugs coming that may be very effective in TP53. So, we are checking for that. Those drugs are in trials, but the trials are showing very promising data and could be a great option if a patient is known to have a TP53.

Those drugs are Magrolimab, CD47 antibody, and APR-246. So, these are the four most important therapeutic mutations.

There are also some mutations that have prognostic value even though we cannot target them. These include mutations like RUNX1, DNMP3A, ASXL1.

One does not need to know the list. But the point is that these mutations may help determine whether a patient falls into intermediate-risk group or high-risk group, which then impacts the decision as to whether we need a stem cell transplant or not. So, it really is important to get this molecular profiling. It’s actually available in the United States commercially. And any clinic or hospital is able to actually order it. And insurance will cover it in 100 percent of the cases.

Katherine:                   

Wow, that’s great. What should – when should patients be tested, and how is testing done?

Dr. Daver:                   

Yeah. So, the basic testing for any suspected new acute leukemia is to get a bone marrow biopsy. That has to be done.

That should be done very quickly because all of the information that will be generated to make the treatment decision will come off the bone marrow biopsy.

Katherine:

What about retesting, Dr. Daver? Is that necessary?

Dr. Daver:                    

Yeah. So, retesting is necessary in – not for everything, I think.

But let’s say someone had treatment induction and relapsed a year later. So, we would definitely retest: 1) to confirm with the bone marrow’s relapsed AML, get the blast percentage because we need that before restarting treatment, so we know what was the starting point to know how the patients doing after treatment if he’s responding. 2) Molecular testing, for sure, should be repeated. We usually repeat the molecular testing such as FLT3, IDH1, IDH2, because there are drugs that can target these mutations in a relapse.

And more interestingly, we actually have published, and other groups have also published, that there are some patients who may not have those mutations at baseline but may actually acquire or have detectible mutations at relapse. So, if you don’t have FLT3 at baseline, your physician may assume that the FLT3 is not there, not do mutational testing. But in fact, that may not be true. So, it is important to retest about 15 percent, one five percent, in our publications can acquire a detectible FLT3. Which is critical because this could then change your treatment.

IDH1 and two are rarely lost or acquired, but we have seen a few five percent or so cases of that. So, it’s still better to check for that. And then TP53 we check for because now we have these new research clinical trials, phase one, two, that are showing some very encouraging activity in TP53. So, these are probably the main things to retest for.

There’s also some new clinical data emerging with a new drug called menin inhibitor that targets a particular chromosome abnormality, MLL rearrangement. This is again in a phase one setting, so the data may not be widely disseminated. But we’re seeing some very encouraging activity with menin inhibitors.  

And so, we are 100 percent checking for the MLL rearrangement chromosome, which can be done on FISH, or routine chromosome.

And if that is there then trying to get on one of the menin inhibitor trials, they’re opening about 25, 30 centers with different menin inhibitors, would be a very, very good option because we think these will be the next molecular or chromosome-targeted breakthrough in AML.

Katherine:                   

We’ve been discussing how molecular testing results lead to targeted therapy. How do targeted therapies work?

Dr. Daver:   

Targeted therapy means that we’re targeting a particular mutation. Now we may be targeting in different ways. So, some of the drugs, like FLT3 inhibitors, these are the most established and oldest targeted therapies in acute myeloid leukemia, been in development for about 18 to 20 years, work by blocking a particular receptor, the FLT3 receptor.

That receptor, when blocked, removes the growth and proliferation signal to the leukemia blast. And that receptor is much more preferentially and heavily expressed on the surface of the acute myeloid leukemia cell as compared to the normal, healthy myeloid or lymphoid cell. So, basically, we are shutting down the growth signals, resulting in eventual death of the leukemia blast and that’s how FLT3 inhibitors work. So, it’s a more of a direct activity resulting in cell death over a few days and quick action. On the other hand, we have what also is called targeted therapies but act very differently. These are IDH1, IDH2 inhibitors.

So, when you use an IDH1 or two inhibitor, they do go to the IDH1 and two receptor on the surface of the acute myeloid leukemia cell, but actually, they don’t result in the death of the cell. They actually cause what we call differentiation.

So, they promote that immature abnormal leukemia cell to undergo maturation and become a normal myeloid cell, which, over time, will die because normal cells have a finite lifespan, and they will die. As compared to leukemia blasts, which can live on much, much, much longer. And so, this process is called differentiation. So, FLT3 inhibitor, very different direct cell death. IDH inhibitor, very different from most maturation differentiation of immature cells to mature cells and takes longer. So, this is important clinically because with FLT3 inhibitors. We see responses quickly, one to two months. IDH inhibitors it takes longer, three to five months.

And so, targeted therapy is not one and all the same. You may be targeting a particular receptor, but the modality of action downstream may be very different.

Katherine:                   

What’s the treatment regimen for targeted therapies, and how long are patients treated with these types of therapies?

Dr. Daver:   

Yeah. I mean, that’s an area of big research. There’s no one field of answer yet for – and I don’t think there will be.

Of course, eventually. So, it really depends on; 1) What setting we’re using it in? Newly diagnosed, relapsed AML. In relapsed AML, with most targeted therapies, whether you’re use is a single agent, like FLT3, IDH1, IDH2, TP53, MLL-targeted agents, the goal is to get a patient to transplant.

Transplant, meaning allogeneic stem cell transplant using a sibling donor or a match-generated donor.

Because in relapsed AML without transplant, irrespective of the genetics and chromosomes, all relapsed AML have very poor outcome. The survival is only 20 percent or less without transplant.

If we can get a patient to transplant, we do have a good chance of long-term survival. So, the goal is transplant. And we usually use a targeted therapy for short, finite period, two to four months, to get a remission, get to transplant, hope that will cure the disease.

In front line, it’s quite different. We’re using induction chemotherapy with FLT3 inhibitors. In some research trials, we’re adding IDH1 and two inhibitors. We’re using Venetoclax, which is a kind of a targeted therapy.

Also, the BCL2 in combination with hypomethylating agents. And here, the targeted therapy is often used indefinitely. At least for one or two years. But in our approach and our guidelines, we continue the FLT3 inhibitor, IDH1 or two inhibitor or Venetoclax, as long as patient is tolerating it and does not have disease progression.

So, these are being used kind of similar to CML, chronic myeloid leukemia, where we use tyrosine kinase inhibitors or myelofibrosis, where you use jak inhibitors. They don’t cure the disease, but they continue to control the disease as long as you take them.

And in the end, we call this functional cure.

If somebody takes a FLT3 inhibitor and lives 20-plus years, semantically, he was never a cure, like an infection gets cured. But functionally, to me, he lived a normal life, and he was cured.

Dr. Daver:                    

And so, that’s how we’re using those inhibitors in the frontline setting different from the relapse setting.

Katherine:                   

How do these newer therapies differ from more traditional chemotherapy?

Dr. Daver:   

Yeah. Dramatically different. Completely different from traditional chemotherapy. So, to put it in more layman terms, traditional chemotherapy is like a nuclear bomb. Right? You – There’s a lot of things there in the marrow. You don’t know what’s good. You don’t know what’s bad. Blow it all up and hope that, when the new plants grow, the good ones grow and the bad ones were kill. And, in fact, this is true, to a large extent. Traditional chemotherapy, not to put it down, is actually been curative in a large population of AML for the last three decades. Our group and British MRC and Polish, and many groups have published up to 50 to 65 percent cure rates, especially in younger patients, below 65, with traditional chemotherapy.

So, this is not bad. People always get depressed with leukemia. But if you look at solid tumors, I mean, they have never achieved cure rates above 10 to 15 percent till the last decade or so. So, we were still getting 60, 65 percent cure rate. Two out of three.

So, traditional chemotherapy has done great work. But it was that approach. Just nuclear explosion. Take it all out, and hope good stuff comes.

Now the targeted therapy’s like a sniper. It’s actually looking for the particular leukemia cells and trying to take them out one by one with minimum collateral damage to your healthy bone marrow cells, which are important to produce red cells, platelets, white cells. So, guess what? There’s much less toxicity. You don’t see the hair loss with these agents. You don’t see the mouth sores and mucositis. GI complications are much less; infection risk is usually less.

Not to say they don’t have their own side effects. Unfortunately, even the targeted therapies have unique side effects. But, in general, those side effects are much less impactful in a negative quality-of-life way and much more manageable and tolerable. So – And, in the end of the day, they’re actually often more effective.

So, for example, with the FLT3 inhibitor, the study that was done with Gilterinib and Quizartinib, two very potent FLT3 inhibitors, was looking at a single-agent FLT3 inhibitor versus three-drug, high-intensity combination nuclear chemotherapy. And if I told this to any layperson, they would say, oh my God, that’s completely unfair comparison. You’re going to use three drugs, IV chemo, strong chemo, and compare it to one oral targeted pill. There’s no way the pill can be even equal, leave apart, win.

But guess what? The targeted therapy actually won. It not only was equal. It doubled the response rates, it reduced the toxicities and early mortality and led to improved overall survival, the gold standard. So, this shows that even though they are sniper, they can actually be much more effective with less toxicity. So, it’s a win-win. Better, tolerable, and more effective. Now the next stage within then decade, we think, it’s not one or the either, it’s really a combination. So, we’re reducing the dose of chemotherapy. So, we’re not making it as nuclear as it was. It’s still intense. But much more tolerable. And we’re compensating for that by adding the targeted therapy.

And, in fact, in the end, we expect much higher responses and survival with much better tolerability and lower early mortality. But I don’t think we’re at a stage where traditional chemotherapy is gone. Maybe 10, 12 years from now, as many more developments come, we’ll get there. But I think it still has a role, especially in the younger AML patients.

Katherine:                   

Dr. Daver, you mentioned the – some common side effects of chemotherapy. What about some of the newer therapies? Do they also have side effects?

Dr. Daver:                    

Yeah. Absolutely. I mean, every therapy we have in leukemia has a side effect. There’s no drug I can mention that is just devoid of them. Of course, some are less, and some are more. So, to be more specific, I think, for example, IDH1, IDH2 inhibitors, these are probably one of the most tolerable treatments we have in all of leukemia treatment. In general, they don’t cause much myelosuppression. Meaning, drop in blood counts. They don’t cause hair loss. They don’t cause mouth sores and GI upset in majority of people.

They’re always some patients who may. But what they can cause are two things: Number one, is they can cause what we call the differentiation syndrome.

And differentiation syndrome means the blasts that are going from the immature state to the mature state; in that process, they can cause an inflammatory reaction. And this can manifest with fever and cough, and chest pain, hypoxia. It’s something that’s actually very, very easily treatable, giving steroids for three or four days will take care of it. But many times, people were not aware of this. And so, often, we saw this was missed in the community.

So, that’s one specific example. With the FLT3 inhibitors, sometimes we see that they can cause more prolonged drop in blood counts, and count recovery can be delayed. Or we can sometimes see that they may cause some cardiac signals; increase in cardiac intervals. Again, something that, with close monitoring, bloodwork, keeping the electrolytes normal, can be managed. But I don’t want to go through the whole list. But the point is that there are specific and unique side effects that can be seen with particular targeted therapies.

And again, this is a learning curve where we have done these trials for eight to 10 years. So, we became familiar. But when the drug is approved, it’s a – it’s kind of a night-and-day situation in the community. They didn’t have the drug yesterday. They have it today. But there may not be any learning curve there. So, I think that’s where a lot of education and interaction with our colleagues is now coming into play.

But also, patients, I think, need to take this a little bit into their own hands, and also read about the label, read about the drug. So that, if they have side effects, if they actually ask their doctor and say, do you think this could be differentiation? I read about it. Yeah, most people will at least think about it. And I think this could be helpful to make sure that things are not missed. So, we do want patients to be more interactive and kind of  take things into their own hand. Because there are so many new drugs out there that their doctors may not be fully familiar yet.

Katherine:                   

Well, let’s talk about patient advocacy. What are some of the key tests that patients should ask for after they’ve been diagnosed?

Dr. Daver:                    

Yeah. Absolutely. So, I think the key things that patients should want to get the information is: 1) Knowing the bone marrow blasts.

I mean, that’s really basic. Just knowing what leukemia it is. What are the blast percentage? 2) Is, I think, chromosome analysis is very critical to get that information and to make sure we’re not missing acute promyelocytic leukemia, or core-binding factor leukemia, which have different treatments and very favorable outcomes, and would never, in general, never require a allogenic transplant. At least in majority of cases.

And 3), which is the one where we still see that it may sometimes not be available or be missed, is molecular testing.

I think it’s very critical to request molecular testing. And among molecular testing, especially FLT3, maybe IDH1 and IDH2, and TP53.

So, I think these are the most important data sets. Cytogenetics, key molecular mutations, bone marrow blasts, and confirmation of the type of leukemia before we embark on any treatment.

Katherine:                   

How can patients feel confident, do you think, in speaking up, and becoming a partner in their care?

Dr. Daver:   

Yeah. I mean, this is always a touchy area because physicians may feel that this is kind of encroaching on their territory or telling them what to do. And this is always a major challenge. I think when you go for the clinic visits, just to have a list of your questions written down and having them prepared and prioritizing them.

I always say, have your top-three questions ready.

We’ll try to do the others. But we’ll do the top three. And I think, when you have a new diagnosis of AML, the top three should be: what is the type of leukemia I have, and what are the bone marrow blasts? Number one. Do we have any chromosome and molecular information? Number two. And number three: Are there any specific treatments for my specific AML based on that chromosome molecular information? Or do we need additional information, and can we wait for that safely? I think these are the three very reasonable questions which, I think again, most leukemia experts will automatically be discussing this.

But, I think, for a patient, I think that’s important information to make sure they get before proceeding. If there’s time, the fourth question will be: Is – Are – Do we have a choice between high intensity, low intensity? And if we do, what are the pros and cons? In some cases, there may be a choice. In some cases, it may very clear that high intensity is the way to go, or low intensity is the way to go. But still, I think it’s often good to discuss that with your physician.

So, these are probably the four things one can bring up reasonably without the physician feeling that this is going to take forever, and I cannot discuss this. And then a lot of the AML treatment happens in-patient. So, there will be a lot of time for additional discussion. I tell my patients that, look, once we get the basics and the treatment decided, which is what we do in clinic, then you’ll be in the hospital most of the time. If it’s induction chemo for four weeks. Even if it’s Venetoclax, often they’re admitted for five to seven days, they will have more time then to discuss with the physician, the nurses, on a daily basis, and get more of the nitty-gritty.

Things like diet, exercise, lifestyle. Can I meet friends? I think you should not try to bring those things up right in the first visit. Because that may dilute the key information. So, I think staggering it, keeping in mind that many physicians are extremely busy, and getting that information in pieces over time, is probably productive for you and for the doctor.

Katherine:                   

With Covid-19 affecting all our lives right now, what should AML patients be considering at this time?

Dr. Daver:   

There’s a lot of guidelines on general approaches to managing things in COVID. And all of those guidelines heavily center, as we would think intuitively, on precautions.

Hand washing, minimizing contact, avoiding crowded places, trying to get treatment, potentially locally, if there are equivalent options available. We have not changed any of our frontline – we discuss this a lot every week in our faculty meeting.

This is discussed especially, as you know, because Houston currently is a major center affected heavily by COVID, and so, we have discussed whether we should move in a universal way to lower-intensity therapy for all patients. And we haven’t. And there’s pros and cons to that. When we do induction chemotherapy higher intensity, we, in fact, admit our patients for 28 days.

o, actually, even though it’s high intensity, the patient is more protected because they are in the room. Isolation rooms, sometimes. And they have minimum contact with outsiders. So, with COVID, actually, there’s very little opportunities or chances for them to get it. But the chemo is intensive. So, if they did get COVID, then it could be much more difficult or risky, or even fatal. On the other hand, low-intensity therapy is good because it’s low intensity and the risk of COVID, the frequency may or may not be changed; we don’t know. But the intensity we think could be lower because the immune system has not been suppressed.

However, low-intensity therapy very often is given outpatient. And so, then you have the benefit of lower intensity but the risk that you are going to be driving back and forth to the medical center, getting bloodwork, exposed to people in the waiting room, this and that. So, what we decided, after a lot of discussion among a big leukemia expert faculty in our group, was that we will still decide the optimum treatment based on the leukemia chromosome, molecular, age, fitness of the patient like we’ve always done.

And then we just have to try to encourage the patients to do as much precautions as possible. The other thing with the COVID, I think is very important is that, even though you may not be able to travel to your academic institution nearby because it’s harder to travel now, it’s still a good idea to try to get a consultation. We are doing a number of phone or email consultation, either directly with the patient, and even more frequently with their community doctor.

So, I get every day, four or five emails from academic even, and community physicians just saying, I have this patient, new AML, relapsed AML, whatever the case may be, here’s the mutation chromosome information, and I was going to do this. But the patient asked that I run this by one of my top academic colleagues. So, maybe MD Anderson. Some, I’m sure, are talking to Sloan. Some are, I know, are talking to Dana Farber. Cornell, whatever it may be. So, you can always request that. And maybe 100 percent of physicians may or may not do that.

And we’re seeing this collaboration actually. One of the positive things of COVID is we’re seeing these collaborations becoming better and better over time.

Katherine:                   

Oh, excellent. If a patient does need to go to clinic for a visit, what safety measures are in place?

Dr. Daver:   

Yeah. So, there’s a few things we’re doing in clinic is; one is we have staggered our clinics. So, instead of having everybody come at 9:00 or 10:00 a.m., and having 30 people in the waiting room, we really have more time slots.

And we ask people to come three of them at a time in the waiting room. We’re minimizing it three to five patients at most

Of course, there’s a lot of sanitization, dispensation units everywhere, encouraged to use those. The other important thing which, unfortunately, is a double-edged sword, is that we have had to minimize the number of friends, relatives, spouses, that can come with patients.

In fact, the policy at MD Anderson, like most cancer centers, is that nobody is allowed with the patient unless the patient is physically really impaired, as in wheelchair-bound or cannot go to the restroom. Of course, there are exceptions. But generally, I know, and I actually benefit a lot from it too, when patients have their family because the emotional support also helps our medical team to get information across. The patient may be sometimes stressed and forget things. So, what we’re doing more and more is doing phone calls.

So, what I would recommend is, as soon as doctor comes in, say, hey, doctor, can I call my daughter or my wife? I want her to listen to everything. Perfect. I don’t mind. There’s a speaker on. Good.

So, that helps with communication. But those are the big changes we have done from the clinic perspective. Still seems to be working relatively smoothly. We’re still seeing almost about the same number of patients in clinic that we were before COVID. And we have, fortunately, and knock on wood, not seen big numbers of leukemia patients with COVID. And we think the primary reason is because leukemia patients are just very cautious from the beginning. Even before COVID, they knew the risks, and we want them to continue that as much as possible.  

Katherine:

Dr. Daver, thank you so much for joining us today.

Dr. Daver:   

Thank you very much. Always a pleasure.

Katherine:

And thank you to all of our partners.

To learn more about AML and to access tools to help you become a more proactive patient, visit powerfulpatients.org. I’m Katherine Banwell – Thank you, Dr. Daver.

Confused About AML Genetic Testing and Treatment? What You Need to Know

Confused About AML Genetic Testing and Treatment? What You Need to Know. from Patient Empowerment Network on Vimeo.

What is AML genetic testing? Dr. Alice Mims explains genetic testing in AML, including the necessity of testing, the effect on treatment decisions, and why patients should be retested over the course of their disease.
 
Dr. Alice Mims is a hematologist specializing in acute and chronic myeloid conditions. She serves as the Acute Leukemia Clinical Research Director at The Ohio State University Comprehensive Cancer Center – James.

See More From INSIST! AML

Related Resources

 

How is Acute Myeloid Leukemia (AML) Treated?

 

Effective AML Combination Treatment: Pairing Old and New Therapies

 

AML Genetic Testing Explained

Transcript:

Dr. Mims:

So, in regards to older treatments and being effective, seven plus three, which is an intensive chemotherapy, is still the standard of care treatment for patients with favorable risk AML, if they’re candidates for intensive treatments because it is potentially curative. And 7 + 3 is also the backbone for newly diagnosis for patients with FLT3 mutations, we add a FLT3 inhibitor called Midostaurin onto that, as it’s shows to improve overall survival with the addition of that compared to just the chemotherapy alone.  

And also, hypomethylating agents, which are a less intensive treatment, were the standard of care for patients who couldn’t tolerate intensive chemotherapy.  

And now we’re seeing the addition of other agents being added to this, like the BCL2 inhibitor of Venetoclax 

And recent data in phase 3 trial comparing the hypomethylating agent alone versus adding that agent did show an overall survival advantage. And so, these are definitely evolving, and I think as we are learning more about targeted therapies and how they can best be used in combination with chemotherapy other than single. Agent. But you give two targeted therapies together and having even better outcomes. We hope we continue to make improvements from where we were even just five years ago and do a better job for. 

How is Acute Myeloid Leukemia (AML) Treated?

How is Acute Myeloid Leukemia (AML) Treated? from Patient Empowerment Network on Vimeo.

 When diagnosed with Acute Myeloid Leukemia (AML), understanding available treatment options can be overwhelming. Dr. Alice Mims, an AML specialist, provides an overview of AML therapies and discusses factors to consider when deciding on an appropriate therapy with your healthcare team.

Dr. Alice Mims is a hematologist specializing in acute and chronic myeloid conditions. She serves as the Acute Leukemia Clinical Research Director at The Ohio State University Comprehensive Cancer Center – James.

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Transcript:

For the past 30 years, we’ve had the same treatment options, which have been standard intensive induction chemotherapy that weren’t really tailored to individual patients and had significant toxicity. And not necessarily effective for all AML genomic subtypes.

Now we have quite a bit added to the treatment arsenal for AML, including continuing intensive induction chemotherapy for patients who are appropriate. There’s also been the addition for newly diagnosed patients for hypomethylating agents and a new BCL-2 inhibitor called Venetoclax. IDH inhibitors for patients with IDH1 and IDH2 mutations. The addition of FLT3 inhibitors for patients either newly diagnosed or with relapse or refractory disease.

And liposomal daunorubicin and cytarabine in for patients with AML with MDS related changes or therapy related AML that are newly diagnosed. Lastly, there’s also a hedgehog inhibitor, glasdegib, that’s been approved for newly diagnosed AML patients in combination with low dose cytarabine.  

So, when working with patients, there are multiple factors that we take into consideration when coming up with a treatment decision together and it really should be a team approach. But one of the most important things is trying to understand the patient’s goals of care.

Because different treatments have different expectations, side effects, toxicities that we want to be sure we’re all aligned when we’re making a treatment decision together. Also, other features that we take into account can be age. Other comorbidities, including other diagnosis such as cardiovascular disease, diabetes and other medical issues patients may have.

So, for roles that patients have in making these decisions, they should know that they’re their own best advocate. And so, as you’re getting to learn your oncologist who’s helping you make these treatment decisions, it’s very important that you talk about things that are important to you in regards to quality of life, overall goals for your life. Ask questions in regard to side effects and expectations for outcomes for potential treatment. Whether they’re curative or more palliative, which can extend life. And for quality of life, it may not be curative for AML.  

So, AML really was considered a single disease 30, 20 years ago. Now we really know it’s likely dozens of diseases based off of looking at molecular features of an individual patient’s AML. So, it’s very important to try to understand what genomic features your AML may have, meaning DNA mutations that are just present in the leukemia cells. Chromosomal changes as well. And then understanding if, based off that information, that that may afford you additional treatment options other than the current standards of care.  

Effective AML Combination Treatment

Pairing Old and New Therapies

Effective AML Combination Treatment: Pairing Old and New Therapies from Patient Empowerment Network on Vimeo.

With advances in AML research and a number of new treatments, can older therapy types still play a role in care? Dr. Alice Mims discusses pairing early AML treatments with new agents to boost their effectiveness.

Dr. Alice Mims is a hematologist specializing in acute and chronic myeloid conditions. She serves as the Acute Leukemia Clinical Research Director at The Ohio State University Comprehensive Cancer Center – James.

See More From The Pro-Active AML Patient Toolkit


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Transcript:

So, in regards to older treatments and being effective, seven plus three, which is an intensive chemotherapy, is still the standard of care treatment for patients with favorable risk AML, if they’re candidates for intensive treatments because it is potentially curative. And 7 + 3 is also the backbone for newly diagnosis for patients with FLT3 mutations, we add a FLT3 inhibitor called Midostaurin onto that, as it’s shows to improve overall survival with the addition of that compared to just the chemotherapy alone.

And also, hypomethylating agents, which are a less intensive treatment, were the standard of care for patients who couldn’t tolerate intensive chemotherapy.

And now we’re seeing the addition of other agents being added to this, like the BCL2 inhibitor of Venetoclax.

And recent data in phase 3 trial comparing the hypomethylating agent alone versus adding that agent did show an overall survival advantage. And so, these are definitely evolving, and I think as we are learning more about targeted therapies and how they can best be used in combination with chemotherapy other than single. Agent. But you give two targeted therapies together and having even better outcomes. We hope we continue to make improvements from where we were even just five years ago and do a better job for.

How Leukemia is Diagnosed

Introduction to Leukemia

Cancer and neoplastic lesions are affecting our lives every day. Nearly 40% of the world’s population is affected by cancer—irrespective of age, gender, and ethnicity. Equally detrimental to cancer’s physical manifestations are the psychological influences. However, medical advancement and new research are helping to to combat this life-threatening disease.

Of all the cancers of the body, the most treacherous is Leukemia. It is a cancer of blood cells. Humans have three kinds of blood cells: red blood cells, white blood cells, and platelets. Leukemia involves the malignant proliferation of white blood cells (WBC).

Our white blood cells are major components of our body’s defense mechanism. They play a vital role in fighting against diseases, whether bacterial, viral or fungal in nature. They originate within the bone marrow, spleen and lymph nodes.

A person suffering from Leukemia has poor white blood cell functioning. WBCs start to divide abnormally eventually outgrowing the normal number of cells.

Leukemia has 4 types:

  1. Acute Myelogenous Leukemia (AML)
  2. Chronic Myelogenous Leukemia (CML)
  3. Acute Lymphocytic Leukemia (ACL)
  4. Chronic Lymphocytic Leukemia (CLL)

1. Acute Myelogenous Leukemia (AML)

Acute Myelogenous Leukemia is a heterogeneous clonal disorder. It is characterized by immature myeloid cells and bone marrow failure. It commonly affects children and adults. Studies have suggested the disease arises from recurrent hematopoietic stem cell genetic alterations.

2. Chronic Myelogenous Leukemia (CML)

Chronic Myeloid Leukemia is a myeloproliferative (slow-growing blood cancer) disorder characterized by the existence of a balanced genetic translocation of chromosomes 22 and 9. It mostly affects adults. CML consists of 3 distinct phases: chronic, accelerated, and blast phases.

The history of patients with CML shows 3-5 years of chronic stage proceeding to a fatal blast phase and then progressing to an accelerated phase.

3. Acute Lymphocytic Leukemia (ALL)

Acute Lymphocytic Leukemia is the second most common Leukemia occurring in adults. Like other Leukemias, ALL’s pathophysiology is also based on chromosomal abnormalities and genetic alterations which happen to take place in differentiation and proliferation of lymphoid precursor cells present in the bone marrow and blood. In adults, the precursors of B- lymphocytes are greater in number than the malignant T- lymphocytes.

4. Chronic Lymphocytic Leukemia (CLL)

Chronic Lymphocytic Leukemia is a tumor of CD5+ B cells that characterizes the deposition of tiny, mature lymphocytes in the blood, bone marrow and lymphoid tissues. Apart from the CD5 cells, other genetic alterations are involved in the pathogenesis of Chronic Lymphocytic Leukemia. Stromal cells, T cells and nurse-like cells in the lymph nodes also predominate.

Causes and risk factors for Leukemia

Although the exact cause of Leukemia is unknown, certain risk factors can contribute to making a person susceptible to it. These include radiation, viruses, exposure to benzene, smoking, genetics, and family history.

1. Ionizing radiations

Exposure to ionizing radiation comes from continuous radiation therapy for treating any pre-existing cancer. Prolonged exposure to X-rays is found mostly in people who work as radiologists and are exposed to persistent radiation. Patients who have received chemotherapy sessions for cancers are also prone to Leukemia. Ionizing radiations damage the DNA and result in the defective genetic makeup of stem cells.

2. Viruses

The Human T-lymphotropic Virus (HTLV-1) has been shown to have an association with Leukemia.

3. Exposure to benzene

Benzene is a toxic solvent used in cleaning chemicals and some hair dyes. Benzene’s toxic effects on the blood and bone marrow include increasing the risk of Acute Myeloid Leukemia (AML), myelodysplastic syndrome, and other hematological malignancies, such as non-Hodgkin’s lymphoma.

4. Smoking

Smoking is not only detrimental for the lungs alone but for the entire body. Although the link between smoking and Leukemia is unclear, studies say it can affect the bone marrow and increase the chances of AML in young adults.

5. Genetic conditions

Chromosomal abnormalities are also responsible for increasing Leukemia susceptibility. Examples include Down syndrome, Klinefelter syndrome, Fanconi anemia, Li-Fraumeni syndrome, Bloom syndrome, Ataxia-telangiectasia, and neurofibromatosis, to name a few.

6. Hereditary

The most common cause of Leukemia is family history. If any family member has had Leukemia it increases the risk for other blood relatives.

Signs and symptoms of Leukemia

The signs and symptoms of Leukemia vary with different forms. They are generally nonspecific and warrant investigations for proper diagnosis.

Acute Myeloid Leukemia (AML)

The signs and symptoms of AML are:

  • Fever
  • Pain in bones and joints
  • Pale skin
  • Easy bruising and contusions
  • Recurrent infections
  • Unusual bleeding, epistaxis, bleeding gums

Chronic Myelogenous Leukemia (CML)

The signs and symptoms of CML are:

  • Fatigue and muscle weakness
  • Shortness of breath
  • Pyrexia
  • Increased sweating mostly during the night
  • Cachexia (weight loss)
  • Abdominal discomfort secondary to spleen enlargement
  • Stomach bloating
  • Itching
  • Pain in joints and bone

Acute Lymphocytic Leukemia (ALL)

The signs and symptoms of ALL are:

  • Joint pain and muscle fatigue
  • Fever
  • Frequent infections
  • Epistaxis (Nose bleed)
  • Lumps felt around the neck, groin and underarms as a result of lymph node swelling.
  • Pale skin
  • Shortness of breath

Chronic Lymphocytic Leukemia (CLL)

The signs and symptoms of CLL are:

  • Nocturnal sweating
  • Fever
  • Recurrent infections
  • Fatigue and constant tiredness
  • Cachexia
  • Loss of appetite
  • Stomach bloating as a result of splenomegaly (enlarged spleen)
  • Shortness of breath
  • Pea-sized swelling or lumps in groin, neck or armpits.

Diagnosis of Leukemia

Early detection can prevent complications. The earlier the diagnosis the easier treatment is. Medical advancement has made diagnosis easier than ever before. Some of the essentials to reach an accurate and precise diagnosis are enlisted below.

History and examination

A proper and detailed history is the key to an ideal diagnosis. It involves asking relevant questions related to the signs and symptoms that can link to the suspected disease.

Your physician might ask the following questions:

  1. How long have you been feeling a fever?
  2. What is the temperature?
  3. Do you feel a loss of appetite?
  4. Have you experienced prolonged bleeding after a cut?
  5. Have you noticed any changes in weight recently?
  6. When did you notice lumps?
  7. Are these lumps felt, painful and movable?
  8. Did you feel the lumps gradually increasing in size?
  9. Do you face difficulty in breathing?
  10. Do you feel you sweat a lot while sleeping?
  11. Are you taking any medications?
  12. Have any of your family members had any diseases?
  13. When did you feel the need to visit the physician?

The answer to the above questions can lead to the next step, investigations.

Investigations for Leukemia

Investigations are the major component involved in diagnosis as they make the suspected disease clear to understand. These include blood tests, radiology and biopsy.

1. Blood tests

  • Complete Blood Count (CBC)
  • White Blood Cell (WBC) differential
  • Blood smear
  • Tumor markers
  • Cerebrospinal fluid (CSF) analysis
  • BCR ABL1
  • Genetic tests for targeted cancer therapy
  • Chromosome analysis

The most commonly used test is the Complete Blood Count (CBC) which shows a clear picture of the abnormal growth of red blood cells, white blood cells and platelets.

2. Radiology

The excessive proliferation of the cells in the bone marrow leads to marrow expansion and invasion of the cortex which, in later stages, can be seen by radiographic studies. A simple X-ray can reveal any spot bone changes. In some circumstances, a CT-scan may be needed to extensively study the disease and prognosis.

X-ray findings may include:

  • Osteolytic lesions; most commonly seen in Acute Lymphocytic Leukemia seen in small and flat bones, metaphysis of long bones.
  • Metaphyseal bands (classical Leukemia lines)
  • Bone destruction
  • Some pathological fractures
  • Radiological lesions, in later cases, are seen in the form of vertebral collapse, osteolysis of bones and avascular osteonecrosis.

3. Bone marrow biopsy

This is the gold standard investigation to diagnose Leukemia. This invasive procedure is done after the suspicion of Leukemia or when the blood test reports point to a Leukemic picture.

The procedure involves the removal of a small sample of bone marrow from the hipbone. A long, thin is the needle is used to extract the bone marrow. Once the sample has been taken it is sent to the laboratory where the histopathologists study the tissue microscopically.

Prior to examining the histopathologist or the lab technician prepares a slide. During the process, the specimen is then cut into thin slices. The sectioned structure is dyed using different dyes. The dye discriminates against the parts of the cells. The section is then placed on a glass slide and then covered with a slip on the top to keep the specimen intact. The slide is now ready to be placed under the microscope.

The samples examined under the microscope are then studied based on the type of cells, how the cells are arranged, whether the cells are normal or abnormal etc.

The microscopic findings may reveal:

  • Acute Myeloid Leukemia

Increase in bone marrow cellularity, consisting of granulocytic or monocytic forms a number of erythroid precursors

  • Acute Lymphocytic Leukemia

Hypercellular bone marrow with multiple tightly packed lymphoblasts that have undetectable cytoplasm, round irregular shape, divided nuclei, and dispersed chromatin. The bone marrow has B and T lymphoblasts with indistinguishable morphology along with necrosis in some areas.

Treatment for Leukemia

Treating Leukemia challenges all medical practitioners. Its success and failure solely depend on the extent of the disease and how far has it spread within the body.

Following are treatment options that can help fight Leukemia.

1. Chemotherapy

Chemotherapy is the use of anticancer drugs to kill or halt the proliferation of cancer cells. Generally, chemotherapy is administered orally or intravenously. In some patients, the chemotherapeutic agent is given intrathecally, i.e., injected into the CSF (cerebrospinal fluid) that bathes the brain and spinal cord. This is done after performing a lumbar puncture and injecting chemotherapeutic drugs, such as methotrexate. The course is usually repeated every three weeks.

2. Radiotherapy

Compared to chemotherapy that attacks all the cells of the body, including the healthy ones, radiotherapy is a localized treatment regimen. High ionizing-energy radiation emits to destroy cells that have an increased proliferation rate. Radiotherapy can either be given to cure the disease (therapeutic) or to improve the signs and symptoms encountered during the disease course (palliative).

3. Stem cell or bone marrow transplantation

Transplants are widely used in management and treatment of the disease. Bone marrow is transplanted from a patients’ family member, or another person who bears the same type of bone marrow, into the diseased person. The survival rates vary with different factors but the cost and affordability remain the major concern in this treatment modality.

4. Immune therapy

Immune therapy is another set of treatments that has some promising result in managing Leukemia. The immune therapy works by promoting the immune cells of the body to fight against cancer cells. One of the successful regimens in immune therapy is Gleevec, commonly given in Chronic Myeloid Leukemia. CML patients live a long, symptomless life with the daily oral administration of this drug.

Complications with Leukemia

Though Leukemia is curable, treatments may give rise to certain complications–basically the body’s response to the treatment given. The complications mostly arise from chemo and radiation.

They can include:

  • Anemia
  • Skin rashes
  • Altered taste sensations
  • Soreness of the mouth and throat
  • Liver dysfunction
  • Hair loss
  • Diarrhea
  • Fatigue
  • Bleeding
  • Fertility problems
  • Nausea and vomiting
  • Neurological effects
  • Impaired sexual activity

Relapse of the disease may also occur after some years.

Conclusion

The prognosis of Leukemia depends on how far has the disease has spread but the medical advancement has brought in new regimens that can now treat Leukemia at any stage. A person suffering from Leukemia and undergoing its treatment should be dealt with love, care, and pampering

How to help prevent Leukemia

Informational campaigns and awareness programs help people learn about the risk factors of Leukemia. Family members of Leukemia patients should undergo blood screenings to see if they have been affected. A good diet can help improve health status. Limiting use of benzene-infused chemicals can also make the disease less susceptible. Ceasing tobacco smoking can also help keep Leukemia at bay.

 

References

Acute Lymphoblastic Leukemia

Leukemia: an overview for primary care

Acute Myeloid Leukemia: diagnosis and management based on current molecular genetics approach

Treatment of acute myeloid leukemia

Clonal hematopoiesis and preleukemia-genetics, biology, and clinical implications

No free rides: management of toxicities of novel immunotherapies in ALL, including financial

Adult Acute Myeloid Leukemia Treatment

Acute Lymphocytic Leukemia

Genetics and prognosis of ALL in children vs adults

Etiology of leukemia. A review

Symptoms of adult chronic and acute leukaemia before diagnosis: large primary care case-control studies using electronic records

Acute lymphoblastic leukemia: a comprehensive review and 2017 update

Acute myeloid leukaemia: optimal management and recent developments

Medical Update on Acute Myelogenous Leukemia (AML)

This podcast was originally published on cancercare.org by Mary-Elizabeth Percival, Eytan M. Stein, Carolyn Messner on June 14, 2019, you can find it here.

 

Topics Covered

  • Overview of Acute Myelogenous Leukemia (AML)
  • Current Treatment Approaches
  • Transplantation as a Treatment Option for AML
  • New Therapies
  • The Role of Clinical Trials: How They Increase Your Treatment Options
  • Clinical Trial Updates
  • Symptom, Side Effect & Pain Management Tips
  • Key Questions to Ask Your Health Care Team
  • Quality-of-Life Concerns
  • Questions for Our Panel of Experts

Panel of Experts

Mary-Elizabeth Percival, MD, MS

Assistant Professor of Medicine (Hematology), University of Washington, Assistant Member (Clinical Research Division), Fred Hutchinson Cancer Research Center, Attending Physician, Seattle Cancer Care Alliance

Eytan M. Stein, MD

Hematologic Oncologist, Clinical Trialist, Acute Myeloid Leukemia, Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center

Carolyn Messner, DSW, OSW-C, FAPOS, FAOSW

Director of Education and Training, CancerCare

Fact or Fiction? AML Causes & Symptoms


Dr. Daniel Pollyea, an AML specialist, dispels common myths around the causes and symptoms of AML and shares advice so that you can identify credible resources for information. Download the Program Guide here.

Dr. Daniel A. Pollyea is Clinical Director of Leukemia Services in the Division of Medical Oncology, Hematologic Malignancies and Blood and Marrow Transplant at University of Colorado Cancer Center. More about this expert.

See More From the Fact or Fiction? AML Series

Related Resources

 

How is an AML Treatment Approach Determined?

 

Addressing Common Myths About AML Treatment

 

Fact or Fiction? AML Research and Internet Claims


Transcript:

Ross:

I’m Ross Reynolds. Today we’re gonna be debunking some common misconceptions about the causes and symptoms of AML.

And joining me is Dr. Daniel Pollyea. Dr. Pollyea, could you introduce yourself?

 

Dr. Pollyea:

Yeah. Hi. Good morning, everyone. I’m Dan Pollyea. I’m an Associate Professor of Medicine here at the University of Colorado, where I am the Clinical Director of Leukemia Service.

 

Ross:

I wanna emphasize to you that this program is not a substitute for medical advice, so be sure to consult your healthcare team when it comes to solid information about it. But you will get some background that I think you’re gonna find useful. And you might have some questions as we go along.

 Dr. Pollyea, let’s start out with the basics. What are the causes of AML?

 

Dr. Pollyea:

Yeah. So, Acute Myeloid Leukemia, it’s a disease, a cancer of the bone marrow.

And it’s the result of an accumulation of mutation and chromosomal abnormalities that affect the DNA of a precursor cell in the bone marrow, otherwise known as a stem cell.

And those abnormalities accumulate until that cell can no longer properly mature, and it also can’t properly die. And so, a cell like that just makes copy after copy after copy of a cell until it crowds out the whole bone marrow with these sorta useless, immature cells.

And the end result of that is the failure of the bone marrow, which causes all of the problems associated with this disease. So, biologically, that’s sort of what happens to make this disease occur.

 

Ross:

What are some of the myths that you hear from patients that come in and they say, “Oh, this must’ve caused my AML,” but you have to tell them that’s not so?

 

Dr. Pollyea:

Right. So, I mean, this is one of the most frustrating issues for patients and their families after diagnosis. I mean, it’s a rare disease, only about 30,000 cases a year in the United States. And so, trying to associate a rare disease with external or environmental factors is difficult to impossible. So, although there are a variety of exposures that probably contribute to this disease, we have very little understanding of what those exposures typically are or how that all works.

So, there’s a few things that we know pretty well; large doses of radiation, either associated with like industrial accidents like the Chernobyl disaster, or some of the radiation therapies that patients receive for other types of cancer. Other types of chemotherapy that are used to cure other cancers can contribute to this disease in later years.

We know that there are certain precursor conditions that can evolve to AML, so a person with myelodysplastic syndrome, for instance, has a fairly high chance of someday evolving to develop Acute Myeloid Leukemia. But beyond these sort of a few associations, there isn’t a whole lot that’s known or proven.

 

Ross:

Now there is radiation associated with X-rays, and some people think that X-rays can cause AML. Is that true?

 

Dr. Pollyea:

Yeah.

So, I mean, I think a priori no because millions of people get X-rays every day, and only 30,000 people a year get AML. So, clearly it’s not a simple association between getting an X-ray and developing AML. But I think that there is an unknown interaction between environmental exposures and a person’s individual genetic makeup that makes a person more or less susceptible to developing something like AML with respect to exposure to the environment or X-rays and things.

So, while you cannot say that getting an X-ray will lead to AML, certainly there are some people who are more sensitive to the damage that’s done by something like an X-ray. And so, the best course of action is to be cautious and judicious about your exposure to these things, but not to not get these things when they are medically necessary.

So, that’s the challenging balance.

 

Ross:

Here’s something else we’ve heard, that weed killers can be a risk factor for AML. Is that true?

 

Dr. Pollyea:

I mean, I think there’s a lot coming out now about weed killers and their association with other types of cancers. Again, I go back to the limitation we have in that in only 30,000 people a year in the United States get AML. Millions of people are exposed to weed killers.

We’re statistically never going to be able to make a clear association. I think that there are certainly some risks for some people. Whether you’re that person who’s more susceptible to developing leukemia or any other cancer because of exposure to a weed killer is impossible to know.

So, like all of these things, I think the advice we have is you have to live your life. You have to do your best to sort of avoid things that you can avoid that you think would be… Or that may cause problems. But not to let those things prevent you from living a normal life.

I know that’s not a satisfying answer, but at the moment that’s the best answer we have.

 

Ross:

Is formaldehyde exposure another risk factor for AML?

 

Dr. Pollyea:

Yeah. We think that it is, and kind of along the lines of benzene. But, again, we think that those studies that have shown those types of association show it in very high amounts, amounts that most people in this country would not be exposed to. But I do think, or we do think that there is something to that, to formaldehyde somehow contributing to this.

 

Ross:

What’s the difference between a risk factor for AML and a cause of AML?

 

Dr. Pollyea:

Yeah. So, I think risk factors by definition are things that may contribute to AML. And a risk factor for AML by that definition could be walking down the street and having some exposure to radiation from the sun. A cause of AML is something that is a much more solid sort of well-understood factor.

Like I said before, having myelodysplastic syndrome, there is a high chance that that can evolve to Acute Myeloid Leukemia. And if that happens then the MDS, the myelodysplastic syndrome, could be considered or would be considered the cause of your AML. So, very, very different in terms of the amount of evidence that goes into making those determinations

 

Ross:

Is there a genetic component to this? Can this run in a family?

 

Dr. Pollyea:

Yeah. So, this is a disease of the genome.

So, I mean, in a lot of respects it is a genetic disease. But the question is very different when you ask is this an inherited genetic disease? Is this disease due to a gene that I inherited from a parent or could pass along to a child?

For many, many years, the answer from the medical community was, “No.” This was not considered to be a disease that clustered in families or that could be inherited. We now know that that’s not necessarily the case. There are some very rare cases where this does seem to travel in families or cluster in families. And we’re now beginning to understand who those people are and what those genes are.

But the vast majority of people with this disease did not inherit a gene to contribute to it and cannot pass this along to a child. This is a random, spontaneous event that occurred within one person’s own body and is not traveling within family. So, we’re learning more and more about this, but really, the vast majority of this is not an inherited genetic condition.

 

Ross:

You’ve mentioned gene mutations. What mutates a gene? What causes that to happen that could lead down the line to AML?

 

Dr. Pollyea:

Yeah. Yeah. That’s a great question. Most of the time we do not know the answer to that. These gene mutations occur spontaneously, randomly, and we don’t understand why they happen when they do happen.

And I know that’s, again, not a satisfying answer. It’s very frustrating, particularly patients come in, and, “I’ve lived a healthy lifestyle. I’ve done everything right. I exercise. I eat right. How could this have happened?”

These are things that for the most part are out of the control of a person. These aren’t impacted by your diet or your activity levels, what you eat or don’t eat, what you do or don’t do. That’s a real frustration. In the end, in almost all cases we don’t know or understand why these gene mutations or these, I call them mistakes in the body, occur when they occur. We don’t understand them.

And, Dr. Pollyea, someone asked if benzene can be a risk factor for AML.

 

Dr. Pollyea:

Yeah. So, benzene is one of the sort of rare environmental exposure associations that we do have clear associations with AML.

But the level of benzene that a person would need to be exposed to is really something that hasn’t been seen in this country in a very long time.

We’d be talking about like an industrial accident type exposure in almost all cases, so being exposed to a cleaning solution or some other fairly minor exposure to benzene, we don’t think is enough, in most cases, to prompt this disease. But benzene in very high doses, like an industrial accident, yes, that is something that we understand can certainly contribute or cause AML.

 

Ross:                          

Autoimmune diseases, such as arthritis, can they increase the risk of AML?

 

Dr. Pollyea:

Oh, boy. That is a really interesting one. So, there are papers in the literature that do support those associations. And I know in my own practice I certainly see that trend. So, I do think that there is something there. There is a proven association between autoimmune conditions and myelodysplastic syndrome, which I said before can be a clear precursor condition to AML. So, certainly, that is an association that is a possibility.

It can be a little difficult to tease out whether it’s those diseases that are associated with ultimately developing AML, or the treatments that people get for some of those autoimmune diseases. Those treatments can modulate the immune system in certain ways that may, in fact, contribute or drive the disease. So, that’s a difficult thing to tease out.

But in general terms, yes, I think there are some associations. Now not by a long shot everyone with an autoimmune disease gets AML. It’s a teeny, tiny fraction. But I think there is an association there.

 

Ross:

How easy is it to diagnose AML?

 

Dr. Pollyea:

Well, I mean, I think there’s very clear diagnostic criteria for AML. But I guess that doesn’t really answer the question. And we certainly have patients who come to us after many months of frustration without a clear diagnosis.

So, those scenarios can play out. Many times AML’s a very dramatic presentation, so people get very, very sick very, very quickly with extraordinarily high white blood cell counts and suppression of all the other blood counts that come from the bone marrow like red blood cells and platelets.

In those cases it’s pretty clear that there is a type of acute leukemia going on. There can be some difficulty distinguishing Acute Myeloid from Acute Lymphoblastic Leukemia; those are sort of like cousins, but very different and treated differently. So, it kinda runs the gamut. I mean, it can be pretty clear, but it’s sometimes missed, so yeah.

 

Ross:

This is a great lead-in to my next question, which is about the symptoms of AML. What should be the warning signs that this might be something you need to get looked at?

 

Dr. Pollyea:

Right. So, at presentation, the main symptoms are reflective of the fact that the bone marrow, the organ that makes all the cells of the blood, has failed.

So, that can cause severe anemia. Signs of anemia: a white sort of appearance, feeling dizzy or lightheaded when standing, short of breath, weak, tired, fatigue. Those are all pretty clear presenting symptoms for AML. Because the bone marrow also is responsible for making platelets that clot the blood, some people will present with a bleeding complication, or a very subtle rash made up of these particular red dots. We call that a petechial rash. And that rash can come on when the platelet count gets very low.

Sometimes a person will present with an infection or infections that don’t go away or don’t clear because of decrease in white blood cells, the infection-fighting cells of the bone marrow. Those are made in the bone marrow and can fail in the setting of this disease. So, those are the most common symptoms at presentation, symptoms that are reflective of bone marrow failure.

 

Ross:

You mentioned that sometimes the presentation could be very dramatic, and it sounds like the symptoms are very severe, very quickly. Is that always the case? Is that often the case?

 

Dr. Pollyea:

That is the case in, I would say, a minority of times. That’s usually the case. It’s more often seen in younger patients with AML. Typically, older patients with AML have a more smoldering course and a much less dramatic presentation, although this sort of very dramatic and dangerous presentation can happen in older patients, but it’s probably something like a third of the time that those very dramatic and medical emergency presentations occur.

 

Ross:

How important is early diagnosis?

 

Dr. Pollyea:

Well, I mean, it’s crucial. I mean, in particular in those cases where it’s a very dramatic and proliferative diagnosis, or presentation. A quick diagnosis and recognition of this condition is very important because the sooner a person starts effective treatment the better the ultimate outcome is.

I would say in general terms that applies to all AML patients, but certainly there’s some degrees of variation. So, there’s some AML patients that when I hear about their case on the phone from a referring doctor, it’s appropriate to see them next week in the clinic.

So, it’s not always a medical emergency, but we would never, even in those next-week-in-the-clinic patients, this isn’t something that can wait for weeks or certainly months. This is something that needs to be addressed fairly quickly.

 

Ross:

What are the best ways to manage those symptoms?

 

Dr. Pollyea:

Right. So, I mean, at presentation, all those symptoms, the best way to manage those are to start treatment as quickly as possible. So, impacting the underlying cause of this disease is the most important and critical factor to getting a person feeling better because all of these problems stem from the disease in the bone marrow, and so everything else that you do to sort of help a person’s symptoms are Band-Aids when you’re not talking about getting to the root cause.

So, that’s at presentation. Now once we start treatment, there are many potential side effects to any number of treatments. And it all is dependent on what treatment you’re getting and other things about you that will make this a significant problem in some cases. And in that setting, we do have ways that we can aggressively manage a person’s side effects.

 

Ross:

Can you manage all of the symptoms? Or can people still be experiencing symptoms even after they’re in treatment?

 

Dr. Pollyea:

Absolutely. So, a person with this disease, depending on how long they’ve had it and some of the features, may not be feeling back to their baseline self for potentially weeks or months after treatment starts in the best-case scenario. So, that can be very frustrating, but a person needs to sort of be able to continue to have a good outlook and stay positive.

Because we are able in many cases to make a big impact on this disease and return a person to their pre-disease quality of life.

 

Ross:

What are some of the myths that you hear, Dr. Pollyea, about the treatment? Some things that people come in to you saying they think that it helps, but there’s no science to back that up?

 

Dr. Pollyea:

So, myths about treatment, so many people have a lot of preconceived notions about the intensity of a therapy that they’re going to be asked to withstand. And although sometimes we do treat this disease very intensively, that’s not always the case, and now we have some very effective lower-intensity regimens that can be used in a variety of different scenarios.

There are a lot of people who have a lot of preconceived notions about a stem-cell transplant or a bone-marrow transplant and whether or not they would be eligible for this based on maybe what they’ve heard from friends or family, or what they’ve seen in the internet.

And those are often incorrect. And so, keeping an open mind about treatment options, and discussing those in detail with your doctor are really, really important.

 

Ross:

You mentioned sometimes it presents in young people, sometimes in older people. What’s sort of typical?

 

Dr. Pollyea:

This is a disease of predominantly older patients, so the median age of presentation is 68. So, that means that over half of the patients are over 68 years old at diagnosis. So, while this does happen, can happen in younger patients, that’s really an unusual situation. This disease is, like I said, it is predominantly a disease of older patients.

 

Ross:

There are some patients who I understand think that supplements can deal with the symptoms of AML. Is that accurate?

 

Dr. Pollyea:

You know, I mean, I think the supplement question is always a challenge. A lot of these supplements, or most of these supplements have never been tested with the rigor of treatments that we’re accustomed to in the medical establishment.

That being said, I won’t deny that some of the supplements can help patients based on what patients’ experiences are and what they tell me. I think what’s really important is just be very open and honest with your doctor about the supplements that you’re taking or want to take to ensure that there are no sort of unanticipated interactions with treatments.

Because I think most doctors are very open to having their patients care for themselves in the ways that they’ve become accustomed to, and they know their bodies very well, and we’re very open to that. But there are sometimes that a drug or a supplement might have a bad interaction with the treatment.

And so, a good example in my practice is antioxidants. So, there’s a lot of literature, a lot of interest in antioxidants as cancer-prevention treatment.

And a lot of that is not well-established, but still I don’t see much harm. But when it comes time to treating a cancer, that’s a very different situation. When we give a patient treatment to try to kill the cancer cells, many times we’re trying to provoke oxidation. That’s part of how these drugs and these treatments work.

So, if you’re taking those treatments, but also at the same time taking antioxidants, there’s the potential you could sort of be cutting your therapy off at the knees, fighting it with one hand behind your back. So, for the period of time when my patients are getting an active treatment, I ask that they don’t take it antioxidant.

And they can resume that in the future in the hopes of preventing another cancer. But the time to prevent with an antioxidant isn’t appropriate when you’re dealing with an active cancer. So, that’s just one example.

 

Ross:

Fatigue could be a symptom of AML, but there are a lot of causes of fatigue.

How do you differentiate between something that really could be AML and something that isn’t?

 

Dr. Pollyea:

Yeah. That’s a challenge because I think these are, as I said, older patients. And older patients have a lot of other medical problems. And older people get fatigued, just that’s unfortunately part of the normal aging process. So, we would usually make an assumption that a person’s fatigue and diagnosis is due to the leukemia, the anemia as a result of the leukemia.

But as we successfully treat a patient if they are responding based on their numbers and other objective criteria, but the fatigue is not improving then I think that’s where we would start to look at other contributing factors, and there can be many, so having an open mind at that point is important.

But at the beginning, this is such a monster of a disease, it’s so overwhelming, I think the focus is usually on assumption that the fatigue is due to the disease or to a treatment associated with this disease.

 

Ross:

This question: is loss of appetite a symptom of AML?

 

Dr. Pollyea:

Yeah. I definitely see that, hear that, so sometimes people come in and they say that. Sometimes it may not be a loss of appetite, but an extreme weight loss, so a lot of different types of cancer, including AML, can cause that, just basically unintentional weight loss.

A person’s not trying to lose weight. They’re eating what they think is their normal amount and they’re losing tremendous amounts of weight. So, those are both potential presenting symptoms with AML. And loss of appetite, unfortunately, can be associated with some of the treatments for this disease. And taste changes, things not tasting good, can all contribute to that as well, so those are all challenges that our patients face.

 

Ross:

How important is to get a second opinion? I mean, are all doctors like you pretty much on the same page when it comes to symptoms and treatment?

 

Dr. Pollyea:

So, this is a challenge. So, the answer to the second question first is unfortunately, no. A lot of this hasn’t quite been standardized. And some doctors, oncologists, cancer doctors, they’ll predominantly be treating the things that are common: colon cancer, breast cancer, prostate cancer. And they will probably only have a few cases of acute leukemia a year.

And so, their approach to this is going to be different than somebody who spends all day seeing patients with AML and thinking about AML.

So, a second opinion is a very nice thing to be able to do. The problem with this disease is that most times it doesn’t afford that opportunity. So, with other conditions you have some time to go out, read about it, talk to some different doctors, get a good plan together.

With AML, often that’s not a possibility. A person is so urgently sick that you have to sorta deal with the resources where you are. The best recommendation I have there, if you do find yourself in a situation where there’s not a lot of expertise is to ask your doctor to just call somebody in the region or email somebody in the region who may have that expertise.

And most doctors all over the country have that sort of resource or partner that they will go to and talk the case through with them, and maybe a transfer to one of those high-volume centers is appropriate.

And maybe that’s not a possibility or appropriate, but maybe you would benefit from just talking… Maybe your doctor would benefit from talking this through. But in cases where it’s not such a dramatic presentation, then yeah, for sure, I think a second opinion can be appropriate. But this isn’t something that can be sort of drawn out for long period of time.

 

Ross:

You know, when you find out something like this, your tendency might be to jump on the web and start searching for AML. How do you vet those sources that you look at? How do you figure out that their – what would be a sign that they’re bogus sources?

 

Dr. Pollyea:

Yeah. I mean, I think this field is so rapidly changing and the treatment that we have, that I would, for the most part, assume that what you’re finding on the web is not relevant and is not an up-to-date resource. So, the resources that I listed, the NCCN, UpToDate, the Leukemia & Lymphoma Society, I should mention.

A very important resource that has up-to-date information, and they have even phone numbers for patients and their families to call to get connected with the proper people in a particular city, so that is a really important resource. But I’d be really, really cautious about what you find on the internet because things are changing so fast in this field. There’s a lot of outdated and misinformation on the internet.

 

Ross:

Well, then there’s outright scams. One of the things you mentioned before we went on is be cautious if someone’s asking you to put money upfront, or if it’s a nonmedical facility. What are some things that people should watch out for?

 

Dr. Pollyea:

Yeah. So, one of the things that is so important in our area is clinical trials and participating in clinical trials. Patients who opt to do this and receive experimental therapies can sometimes get the treatment of the future, get a drug that’s not currently available through the FDA, but may have a lot of promise.

And this is the way that we fight this disease. We’ve recently had an onslaught of approvals for AML and that’s because the patients being willing to participate in sanctioned clinical trials. So, participating in a sanctioned clinical trial is crucial, and it’s always a recommendation of all leukemia doctors.

When you participate in a conventional clinical trial, you’re asked to sign a consent form that explains what you’re doing and why. There is a confirmation that this has been vetted by an institution’s regulatory board that is prioritizing the safety and well-being of you, the patient. This has been approved by the FDA as a clinical trial. Nobody would ever ask you to pay money. That’s not ethical to participate in a clinical trial. Insurance covers whatever standard of care. And the clinical trial covers anything that isn’t.

So, if you find yourself in a situation where you’re not being asked to sign a consent form, where a clinical trial has not been reviewed by a regulatory board, where your doctor is not a leukemia specialist, where the FDA has not sanctioned the treatment, all of those are alarm signs.

Because there are people out there that are preying on patients in a desperate situation, a very difficult time in their life, and giving them sort of false hope and leading them down paths that are not legitimate.

One easy thing to do to sorta check to see if a clinical trial is legitimate is to go onto clinicaltrials.gov.

This is a resource set up by our national healthcare system that now feeds in every legitimate clinical trial from all over the world, needs to be registered on clinicaltrials.gov. So, if you can’t find your clinical trial on clinicaltrials.gov, I would have a lot skepticism and caution about that.

 

Ross:

Like what advice do you have for people when they’re first diagnosed? What are the first things they should try to do?

 

Dr. Pollyea:

Yeah. I mean, that reaction is totally normal and natural. I mean, many times these people are perfectly healthy or have been perfectly healthy, and this news is a complete shock.

And so, it is normal and appropriate to have some period of grieving for the healthy life that you are losing. But I would also, while giving yourself that time to grieve, first, draw on your support system, your family, your friends. Allow them to help you. Accept that assistance that they have. And to be optimistic because we are getting so much better at treating this disease.

I had mentioned before, there has been an onslaught of approvals for drugs in this area the likes of which hasn’t been seen in decades. We have new tools and weapons in our arsenal that we couldn’t have dreamed of even a few years ago.

We in our community are very excited and hopeful about the future and we hope that that will translate ultimately to patients, but being depressed or being down, being scared, all of that is normal.

All of that is expected. Anyone would feel like that. Allowing yourself to have those feelings and emotions is important, as long as it doesn’t get in the way of doing what you need to do to fight this disease.

 

Ross:

It sounds like you’re hopeful about new treatments for the disease. How about a cure? What’s the science? What’s the medical science say about that? Are we getting any closer to that?

 

Dr. Pollyea:

We are getting closer to curing this in more cases. So, like I mentioned before, as bad as this is, we can already cure some subsets of patients. There’s one type of Acute Myeloid Leukemia called Acute Promyelocytic Leukemia, APL. It’s an uncommon form of AML, less than 10 percent.

But we can cure close to 99 percent of people with APL. And APL, 15 years ago, was universally the worst form of acute leukemia to get. So, that dramatic 180 that we’ve seen in APL, we are hoping to translate into other forms of AML.

Some other forms of AML have cure rates as high as 50 percent, 60 percent, 70 percent in the right setting. Sometimes we can cure patients with a stem cell transplant fairly reliably. So, we are very, very hopeful about our ability to continue to make progress and cure more and more and more of these patients. That’s the future that we see.

 

Ross:

Dr. Pollyea, thank you so much. And thank you so much for ending on such a positive note. We really appreciate it. And thank you for joining us for this program today.

To learn more about AML and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Ross Reynolds. Thanks for joining us.

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