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AML Research Updates: News from ASH 2020

AML Research Updates: News from ASH 2020 from Patient Empowerment Network on Vimeo.

AML expert Dr. Jeffrey Lancet shares the latest news from the 2020 American Society of Hematology (ASH) annual meeting. Dr. Lancet sheds light on headlines from the meeting including FLT3 inhibitor research, combination therapies with venetoclax, a promising inhibitor therapy, and shares his optimism about the future of AML treatment.

Dr. Jeffrey Lancet is Chair and Program Lead in the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, FL. He is nationally and internationally recognized for his clinical research in the field of acute leukemias. Learn more about Dr. Lancet, here.

Download Program Resource Guide

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Transcript:

Katherine:      

Hello, and welcome. I’m Katherine Banwell. Today we’ll discuss the latest news from ASH 2020 and how AML patients can advocate for personalized care. Joining me is Dr. Jeffrey Lancet. Welcome. Would you please introduce yourself?

Dr. Lancet:                   

Hi, sure. My name is Dr. Jeff Lancet. I’m at the Moffitt Cancer Center in Tampa, Florida, where I am the Chair of the Malignant Hematology Department. We spend a lot of time treating patients and conducting clinical trials of Acute Myelogenous Leukemia.

Katherine:                   

Okay. Thank you. Dr. Lancet, the American Society of Hematology Annual Meeting just closed. What are the AML headlines from this year’s meeting?

Dr. Lancet:                   

Yeah, so as usual, AML was a very busy area for clinical presentations this year at the ASH meeting focusing largely on novel and targeted therapies.

I don’t believe that there were many practice changing developments per se, but rather discussions about many promising therapeutic strategies that are still under development and moving forward rapidly largely in the areas of targeted therapy, low intensity therapy, measurable residual disease and things of that nature.

Katherine:                   

What does this research news mean for patients?

Dr. Lancet:                   

Well, I think that there’s a lot to be encouraged about and maybe I’ll take the time to review some of the highlights in what was presented with respect to some of the novel therapeutic approaches that many of our patients can look forward to receiving in the not too distant future.

So, we often talk about you know, targeted therapies and, of course, one of the major targets over the years has been that of mutated FLT3 which is one of the most common mutations in AML.

And at this meeting we saw several presentations on clinical trials resolved to utilizing inhibitors of FLT3, with some emphasis on the most recently approved second generation drug called gilteritinib.

There were I thought three major presentations focusing on gilteritinib and one was an update on a randomized Phase III trial comparing gilteritinib plus azacitidine versus azacitidine alone in newly diagnosed unfit for induction chemotherapy patients with FLT3 mutations, preliminarily showing good tolerability and high composite complete response rates in the combination on.

There was another trial of gilteritinib plus venetoclax in relapsed and refractory FLT3 mutated AML.

And what was interesting was that a very high percentage of patients achieved response with this combination of gilteritinib plus venetoclax, many of whom were heavily pretreated previously and many of whom had also gotten prior FLT3 inhibitor therapy during an early stage of the disease. So, the combination of gilteritinib and venetoclax and this more refractive study, it was encouraging to see these promising responses.

And then we saw some data reporting the effects of gilteritinib in combination with more traditional chemotherapy induction with a couple of studies demonstrating both a high complete response rates as well as high rates of mutation clearance of the FLT3 mutation.

So, those were very encouraging data that were presented with respect to the FLT3 mutated AML population.      

So, another very important drug that reached the marketplace for AML recently is a drug called venetoclax, which is an inhibitor of a protein called BCL2.

And this drug was recently FDA approved for use in combination with low intensity chemotherapy drugs such as azacitidine or decitabine.

And it seems as though the combination of venetoclax plus one of these hypomethylating agent drugs, azacitidine or decitabine has resulted in very, very strong efficacy signals as recently published in a New England Journal of Medicine paper that reported on the results of the Phase III trial of venetoclax plus azacitidine.

So, that has now become standard of care for older less fit adults with newly diagnosed AML; the combination of venetoclax plus a hypomethylating agent such as azacitidine.

And naturally, there’s been interest in really kind of taking it several steps further to advance the role of these combinations and to also look at additional drugs in combination with venetoclax plus hypomethylating agent therapy.

So, we saw some of that at the ASH meeting this year. One approach would be to take venetoclax and then to combine it with more intensive chemotherapy for perhaps more fit patients or younger patients that could undergo a more intensive program.

So, we saw presentations of venetoclax being combined with a drug called CPX-351, which is a novel liposome formulation of two common chemotherapy drugs that had been approved a few years ago for secondary AML. And we also saw a combination strategy with venetoclax, and a regimen known as FLAG-IDA, which is a commonly used induction regimen in acute myeloid leukemia.

And I think it’s important to recognize that although these trials that combine the venetoclax with more intensive chemotherapy showed signs of good efficacy with good response rates, there were definitely signals of increased toxicity, hematologic toxicity primarily, which is not completely unexpected with venetoclax knowing that it can cause significant lowering of white blood cells and platelets and hemoglobin.

And then finally, there is a lot of interest in, you know, doing these types of combinations with venetoclax in different subsets of AML and one subset of AML that has been very important recently is that of the IDH mutated AML population of patients.

IDH is a fairly common mutation that occurs either in the Isoform of IDH1 or IDH2 and there’s about a 15 to 20 percent incidence of IDH mutations in AML.

Now we do have an inhibitor for both of these types of mutations: ivosidenib for IDH1 and enasidenib for IDH2, but there also appears to be a strong role for venetoclax plus azacitidine in IDH mutated AML.

We saw from a series of patients presented by a physician at MD Anderson looking at outcomes with venetoclax plus azacitidine in IDH mutated AML. And the response rates were very high when you give HMA plus venetoclax to these patients with IDH mutated AML.

But I think more importantly was that there were what we call high intro patient response rates when switching between venetoclax and HMA therapy with an IDH inhibitor containing regimen.

In other words, a patient would have a good chance of responding to the initial therapy and then if or when that therapy stops working, having a good effect from a salvage therapy with the other regimen. So, when you see initially azacitidine plus venetoclax and then had a relapse, the IDH inhibitors worked well and vice versa if you had received an IDH inhibitor and then subsequently received HMA-venetoclax at a later time point that also worked well.

So, it’s encouraging to see that you can potentially sequence these drugs and get continued responses along the way and ultimately we think will help a survivor and keep patients in a better state of health even longer.               

So, I just wanted to take a few minutes also and discuss some of the newer more novel therapies that are really hitting or approaching the landscape right now. One of these is called CC486, also known as oral azacitidine or ONUREG. And this drug was shown in recent literature to prolong overall survival in patients who are in first remission from their AML who had received induction chemotherapy.

So, this drug was used as maintenance therapy after a variable number of consolidation regimens. And people who got this ONUREG or oral azacitidine drug as maintenance therapy, it resulted in longer survival compared to those who had received placebo.

And this was presented at last year’s ASH meeting, but this year’s ASH meeting provided an update, a very important update, showing that the overall survival advantage from this drug, this oral azacitidine drug, when used as maintenance was independent of whether a patient had measurable residual disease at the time that they went onto the maintenance therapy.

In other words, whether you had MRD, measurable residual disease or not at the time of the study entry, your responses were still more favorable, your outcomes were more favorable, if you received this oral azacitidine drug.

So, this was FDA approved earlier this year for patients in the maintenance phase of therapy for AML who had gotten prior reduction chemotherapy.

And importantly, this drug was also shown to be able to convert about 25% of patients who were positive for measurable residual disease; convert them from positive to negative. So, even though they were in remission, they had measurable residual disease and this drug in about 25 percent of the cases converted that from positive to negative. So, that’s a very important finding as well.

Another important drug that I think you should keep your eye on is a drug called magrolimab. This is an antibody against a certain type of protein that is present on the immune system cell called the macrophage, and when this magrolimab drug was combined with azacitidine in a recent clinical trial, it was demonstrated very high response rates of over 65 percent.

And, in particular, in patients with P53 mutations, which is a very bad mutation to have in most cancers, including AML, in patients with this high-risk mutation, the combination of magrolimab with azacitidine appears to be effective based upon the early data that we have with high response rates.

And then finally, I just wanted to make mention of another important area in, not really just AML, but in all cancer and that’s  outcomes disparities between different races and ethnic groups. And we saw a very important presentation at the plenary session this year where the authors reported outcomes amongst younger patients with AML who were African American compared with Caucasian.

And the data clearly indicated a worse overall survival amongst Black patients compared with white patients under age 60. And this included patients who were enrolled in clinical trials. So, that it appeared that African American patients have a worse outcome than Caucasian patients with acute myeloid leukemia highlighting the need to better understand various risk factors and other factors that play into these disparate outcomes between our Black American population and a white American population, which I think could shed light on additional disease characteristics that may help everybody as well.

 

What Does It Mean to Have High-Risk CLL?

What Does It Mean to Have High-Risk CLL? from Patient Empowerment Network on Vimeo.

What does high-risk chronic lymphocytic leukemia (CLL) mean exactly? Dr. Jennifer Woyach explains the meaning of high-risk CLL, factors in determining disease progression, and the impact on treatment decisions.

Dr. Jennifer Woyach is a hematologist-oncologist specializing in chronic lymphocytic leukemia (CLL) at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital & Solove Research Institute. Find out more about this expert here. 

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Transcript:

Katherine:                  

We have a patient question. I have 17p deletion. Should I be worried?

Dr. Woyach:               

So, 17p deletion is usually associated with more aggressive disease biology almost always associated with that unmutated IGHV. The reason I bring that up is there are a very small subset of patients who have 17p deletion and mutated IGHV who, actually, have pretty indolent or slow growing disease.

People who don’t, which is the majority of them with 17p deletion, do have a shortened time to treatment and shortened survival with most of our current therapies. There have been a lot of advances though in the treatment of 17p deleted CLL. And may of our newer therapies can very much prolong the remission time in the lives of patients with 17p deletion.

Katherine:                  

Dr. Woyach, how do these chromosomal changes affect disease progression and prognosis?

Dr. Woyach:               

So, the markers that are associated with more aggressive disease biology usually are going to be associated with people that need treatment within the first few years after diagnosis, especially those people who have 17p deletion, 11q deletion, unmutated IGHV.

Katherine:                  

What exactly are prognostic factors? Would you define that?

Dr. Woyach:               

Sure. Prognostic factors, and I mentioned three of them, the IGHV, FISH, and the TP53 mutation, are ones that have been studied extensively and shown that the presence of this marker or some change in this marker is associated with a change in the biology of the disease or in the response to therapy.

Katherine:                  

How does the identification of these changes or mutations affect treatment options?

Dr. Woyach:               

Well, right now, we’re lucky in CLL because we have a lot of treatment options. I would say the most important changes when we’re talking about somebody with CLL that is about to start their first treatment is the decision of whether chemotherapy is ever appropriate. So, almost everybody with CLL now is treated exclusively with targeted therapies.                              

So, nonchemotherapeutic options. There are some people who are young, and in CLL terms that means under the age of 65, who have mutated IGHV and who otherwise have good genetic list disease. So, normal chromosomes of the 13q deletion, no TP53 mutation. That small subset of patients, actually, has the potential to be cured with a specific type of chemotherapy. It’s called FCR or fludarabine, cyclophosphamide, rituximab. So, for those young, healthy patients, it’s really important to know those risk factors to know if they are in that group that has that potential for cure.

The converse to that is if patients don’t fall in that group, they probably shouldn’t receive chemotherapy as their first treatment, because it’s not as effective as our other therapies.

Katherine:                  

Yeah. It makes sense.

Dr. Woyach:               

And then, even in the future with first and other treatments with novel therapies, we know that patients with 17p deletion and TP53 mutation tend to have a shorter response time. And so, what I use that for in my practice is I know that those are people that I really have to be sure that we’re following them closely, taking any signs of progression seriously, and always have a back-up plan for what we’re going to do if this treatment doesn’t work.

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.

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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.

Events

Fact or Fiction? AML Treatment and Side Effects

When it comes to online Acute Myeloid Leukemia (AML) resources, how do you separate fact from fiction? During this LIVE webinar, Dr. Jessica Altman, Director of Acute Leukemia Program at the Robert H. Lurie Comprehensive Cancer Center, will share her expertise on treatments and side effects associated with AML.

Watch online on Monday, July 1 at 3 PM Eastern (2PM Central, 12PM Pacific) for a 30-minute virtual webinar. Send questions in advance to question@powerfulpatients.org.

Register Here

Fact or Fiction? AML is brought to you by the Patient Empowerment Network. We thank Astellas Pharma US, Inc., Celgene Corporation and Daiichi Sankyo for their support.


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