Posts

AML Targeted Therapies, What’s Available and How Do They Work?

AML Targeted Therapies, What’s Available and How Do They Work? from Patient Empowerment Network on Vimeo.

There are several targeted therapies approved for the treatment of acute myeloid leukemia (AML). Expert Dr. Ellen Ritchie provides insight about recent approvals, how these therapies work, and shares details about newer therapies currently being studied for the treatment of AML.

Dr. Ellen K. Ritchie is assistant professor of medicine and a member of the Leukemia Program at the Weill Cornell Medical College of Cornell University and the New York Presbyterian Hospital. More about Dr. Ritchie, here.

See More From INSIST! AML


Related Resources:

 

Transcript:

Katherine:

You touched upon this earlier, but what targeted therapies or treatments are available for AML patients?

Dr. Ritchie:

So, there have been many recent FDA approvals of drugs that are targeted. One, is the FLT3 inhibitors. And the two that are available are Midostaurin, which is most commonly – was the first drug that was really added to intensive chemotherapy.

And clinical trials show that in those FLT3-positive population that patients had an overall better outcome if midostaurin (Rydapt) were added to intensive chemotherapy. There’s also a drug called gilteritinib (Xospata), and this drug is also a FLT3 inhibitor that was tested in patients who had refractory leukemia. They could either get real chemotherapy regimen or they could get gilteritinib. And it turns out in the FLT3-positive patients, the gilteritinib was superior to the strong chemotherapy. So that’s been approved for patients who have refractory, or disease that didn’t really respond to initial therapy, that is IDH – or is FLT3-positive.

Then there’s the IDH1 and IDH2 inhibitors that have also been approved, and a small proportion of AML patients will be positive for IDH1 or IDH2 mutations.

The IDH1 inhibitor ivosidenib (Tibsovo), is available and can be used to treat patients if you know up front, they have an IDH1 inhibitor. So, that’s a regimen where the single agent can be used to treat an IDH1 mutated patient who’s newly diagnosed. Those patients are also eligible for many clinical trials now, where they’re combining that particular drug with other agents, in an effort to improve outcome. For IDH2 positive patients, there’s a drug called enasidenib (Idhifa). And this drug is used mainly in patients in the second line setting. But it specifically targets IDH2. And patients go into remission sometimes for a prolonged period of time. So, these drugs are FDA approved, and they’re treating targetable mutations.

TP53 mutations are a particularly bothersome mutation because it confers a poor outcome. And I’m happy to say that we have clinical trials now that are available that actually target TP53 mutations.

So, there are – there is therapy available for that type of mutation that was

not available before through the clinical trials. And I expect in coming years that we’re going to see more and more targeted therapies develop in AML which can be used potentially in combination with what we’re already using as backbones to enhance the outcome of patients with this disease.

Katherine:

Well, how do targeted therapies work?

Dr. Ritchie:

So, targeted therapies work on – it’s sort of complicated. The targets which are available, IDH or the FLT3 is really on the outside of the cell and it is a drug which is targeted directly to the FLT3 on the outside of the cell.

It works quite well in the peripheral blood, where you see the blast oftentimes disappear. The big concern always is how well it’s working getting deep into the marrow. But it’s looking at the target on the outside of the cell. IDH1 and IDH2 inhibitors work on particular chemicals which are involved in the kreb cycle, and those of you that took high school chemistry may have memories buried in the deep parts of your brain of learning the kreb cycle. And this is a fundamental metabolic cycle inside cells, and if you have a mutation, an IDH1 or IDH2, you’re unable to go through that full kreb cycle in the appropriate way. And that is something that leads to you having a cancer, in this case AML. So, these drugs actually interfere with what’s happening in that kreb cycle, and allow you to make more normal cells.

Factors to Consider When Choosing an AML Treatment

Factors to Consider When Choosing an AML Treatment from Patient Empowerment Network on Vimeo.

What test results and factors should be considered when choosing an acute myeloid leukemia (AML) treatment? Expert Dr. Ellen Ritchie explains how test results impact AML prognosis and treatment – and other factors that come into play when determining a treatment approach.

Dr. Ellen K. Ritchie is assistant professor of medicine and a member of the Leukemia Program at the Weill Cornell Medical College of Cornell University and the New York Presbyterian Hospital. More about Dr. Ritchie, here.

See More From INSIST! AML


Related Resources:

 

Transcript:

Katherine:

How do the results of these tests affect prognosis and treatment?

Dr. Ritchie:

Well, when a patient has AML, if they are a fit patient, if it will help us determine after initial induction, whether to cure the patient we need to do a bone marrow transplant, or we can just continue with chemotherapy.

And those are really important things to determine. So, if you have a good prognosis AML, if you have an AML that has certain translocations like inversion 16 or 821, or if you have a CEPBA mutation or you have an NPM1 mutation, and that’s all you have, you may do particularly well with chemotherapy treatment alone. And you won’t need to have a bone marrow transplant.

If you have certain other mutations, we know that the only way that we’re going to cure you, is with a bone marrow transplant. And if you are fit, when we finish induction and even as we’re doing induction, we’re preparing you for a bone marrow transplant down the line.

One disadvantage, just to mention about the molecular testing, is it doesn’t come back as quickly as some of the other testing. So that you will have already started induction chemotherapy most generally before the mutational testing comes back. Which can be anywhere – depending upon the institution, between seven and 21 days. So, it takes time for those results to be available.

Katherine:

Outside of test results, Dr. Ritchie, what other factors should be considered when choosing treatment?

Dr. Ritchie:

So, you want to choose whether a patient is most likely to benefit from intense induction chemotherapy. With strong chemotherapies where the backbone of those therapies would be an anthracycline, like daunorubicin (Cerubidine) or cytarabine (Liposomal), or daunorubicin or idarubicin (Idamycin PFS), together with cytarabine. And these are intensive chemotherapies. Versus, non-intensive chemotherapy which is able to be done as an outpatient, more frequently. And it is something that is gentler for a patient, they’re less likely to have severe toxicity. And the backbone of those regimens is using a drug called azacitidine (Vidaza) or decitabine (Inqovi), together with a second drug called venetoclax (Venclexta).

So, these are the two backbones, there may be clinical trials or there may be targetable aspects of your leukemia, which drugs would be added to either of those backbones. But those are the two backbones. And I also like to identify those patients that may not benefit from chemotherapy at all. And so, it’s very important, I think to really get to know your patient. And I spend time with my patient, particularly on the first visit, to understand not only their physical health, but their mental health. How good is their cognition, what is their mood, are they depressed, or are they happy people? And what is their circumstance? Do they have people to support them? Do they live close to family? Is a caregiver able to come, with an elderly patient for example, to visits?

Those, and whether or not they’re living alone and need tremendous support. So that’s really important to determine and helps me to choose what the best therapy might be. And also, concurrently what I can do to shore up the patient to do better with whatever therapy that I’m giving them. I.e., if you’re depressed, let’s work on that, or if your blood pressure is too high, or if you are – your diabetes is out of control at the same time that I’m seeing you, to try and fix those particular problems. In older patients I often do sort of a miniature version of the geriatric assessment. And in trials that have been so far, the most important aspects of the geriatric assessment, are really what is your cognitive function? Do have a mild dementia, or do you not have a mild dementia? Because dementia may be or mild dementia may be associated with poorer outcome.

The other is, are you able to do what we call the incidental tasks of daily life. So, you know fundamental tasks are really brushing your teeth and combing your hair, and dressing yourself. But are you able to do your cooking and your shopping and your banking and those things? Patients who have trouble doing their cooking and shopping and banking, and those types of activities, that also has been associated with a poor overall survival in AML. So, it’s really important to determine all of those aspects and if there are any deficiencies, to really know that the only therapeutic choice for that particular patient would be a low-intensity therapy.

Understanding Personalized Medicine for AML

Understanding Personalized Medicine for AML from Patient Empowerment Network on Vimeo.

What should you know before deciding on treatment for YOUR AML? AML specialist Dr. Ellen Ritchie reviews key factors that guide treatment choices, including biomarker testing results, and shares advice for partnering with your team to advocate for the best care.

Dr. Ellen K. Ritchie is assistant professor of medicine and a member of the Leukemia Program at the Weill Cornell Medical College of Cornell University and the New York Presbyterian Hospital. More about Dr. Ritchie, here.

See More From INSIST! AML


Related Resources:

 

Transcript:

Katherine:

As we begin to talk about personalized therapy and AML, let’s start with the basics. How would you define personalized medicine?

Dr. Ritchie:

Personalized medicine, to me is really, it’s a difficult question. It’s trying to find the best treatment for a particular patient. And it’s looking at biologic issues, what kind of cancer, what type of AML is it, what are the specific mutations or chromosomal abnormalities. But it’s also looking at the person. Is the patient active or not active? Do they have lots of other diseases like diabetes and coronary artery disease? Or pulmonary disease, or are they completely healthy?

Or, do they have support at home? If they’re sick at home is there someone who can take care of them, versus a situation where you’re older and alone and you have no real family member to rely on. So, all of these things are very important in making a personalized decision as to how you treat a patient.

Where Do Clinical Trials Fit Into an AML Treatment Plan?

Where Do Clinical Trials Fit Into an AML Treatment Plan? from Patient Empowerment Network on Vimeo.

AML expert Dr. Eunice Wang discusses the role that clinical trials play in advancing research, the benefits of participation in research, and explains why she recommends trials for AML patients. 

Dr. Eunice Wang is the Chief of the Leukemia Service and Professor of Oncology at the Roswell Park Comprehensive Cancer Center in Buffalo, New York. Learn more about Dr. Wang, here.

See More From Engage AML


Related Resources:


Transcript:

Katherine:

Where do clinical trials fit in when it comes to choosing treatment?

Dr. Wang:

Clinical trials are the mainstay of everything that we do in cancer care. Every single cancer drug that we’ve developed dating back into the 1970s at the National Institute of Health is the result of some patients and some doctors designing a clinical trial. These FLT3 inhibitors were developed over the last several years, so when I first came out of fellowship and started my training, we didn’t have these targeted therapies. Since 2017, in four years, we’ve had nine different drugs approved.

So, clinical trials are the way that we go from a finding in the laboratory to somebody having an extra birthday or going to their son or daughter’s wedding. That’s really how important it is, and those brave individuals who participate in clinical trials are helping not only themselves, but helping other people. I can’t tell you how many patients I enroll in clinical trials for AML, and I have told them – I said, “These nine drugs that we approved were because of nine different clinical trials which demonstrated benefit involving hundreds of thousands of patients.”

I can’t tell you how many times I’ve had a patient say to me, “Look, doctor, I’m going to participate in this clinical trial so that even if I’m not helped, you could learn something from me that could help the next person with their disease.” People are incredibly unselfish when it comes to clinical trials. I recommend a clinical trial for all my patients because I feel like that’s the cutting-edge clinical care.

I had patients here who I had on clinical trial drugs, and I was able to go to them and say, “Good news: Your drug has now been approved.” And, they say, “Doctor, why? I’ve been on this drug for a year.” And, I said, “That’s right, because you were part of that clinical trial, and you’re here now because of that drug, and now, a year or two later, that drug’s potency has been recognized, and now, the fact that you were in that trial has really helped us get this approval, which is going to help every other patient with that disease going down the line.” So, very important.

AML Research and Emerging Treatment Options: An Expert’s Perspective

AML Research and Emerging Treatment Options: An Expert’s Perspective from Patient Empowerment Network on Vimeo.

AML expert Dr. Eunice Wang shares exciting advances in the field of AML research, particularly in targeted therapies related to the TP53 and NPM1 mutations. 

Dr. Eunice Wang is the Chief of the Leukemia Service and Professor of Oncology at the Roswell Park Comprehensive Cancer Center in Buffalo, New York. Learn more about Dr. Wang, here.

See More From INSIST! AML


Related Resources:


Transcript:

Katherine:

What specifically are you excited about in terms of AML research and emerging treatment options?

Dr. Wang:

I am really excited about the advent of newer targeted therapies. Right now, we only have targeted therapies for probably about three mutations out of the many, many mutations that we know exist in AML. So, we know that there certainly are patients that have specific mutations, such as TP53 mutations, or patients who have very complicated series of DNA damage, that just don’t do well with any of our therapies.

I’m looking forward to another bunch of targeted therapies – these inhibitors called menin inhibitors – that might be useful for treating patients that have mutations in NPM1 gene or other chromosome abnormalities.

I’m also really looking forward to us being able to finally unleash the power of the immune system for treatment of AML with a few novel agents coming down the pike which have, for the first time, started to show that immune modulation can work in AML patients.

What Key Tests Do You Need Before Choosing an AML Treatment?

What Key Tests Do You Need Before Choosing an AML Treatment? from Patient Empowerment Network on Vimeo.

How do test results influence treatment choices for AML? Dr. Eunice Wang shares information about essential testing and explains how results aid in determining the best personalized treatment option for each patient.

Dr. Eunice Wang is the Chief of the Leukemia Service and Professor of Oncology at the Roswell Park Comprehensive Cancer Center in Buffalo, New York. Learn more about Dr. Wang, here.

See More From INSIST! AML


Related Resources:

 

Transcript:

Katherine:

What is the role of testing when deciding on treatment for AML?

Dr. Wang:

Testing is essential in us selecting and determining the best personalized treatment option for each individual patient. As you know, AML is an aggressive hematologic malignancy and can be devastating, both in its life-threatening nature and in its rapidity and the need for a rapid diagnosis. Testing, including both pathology results as well as protein marker testing, and, importantly in this day and age, DNA and RNA testing is essential because we have numerous different treatment options that could be available to the patient if their particular disease biology matches with the targeted therapies that we have.

So, as you may or may not know, since 2017, we’ve had eight or nine different therapies approved for AML, and this is a bonanza of options, some of which are only for specific biological subsets, and some even for specific patients, such as those above the age of 75. So, doing that testing, particularly that genetic testing, is important both in establishing the diagnosis and determining whether there is less toxic, more targeted, personalized treatment approaches, some of which involve low-dose chemo or even pills available to the individual patient.

Katherine:

You’ve answered this, in part, but which tests are essential following an AML diagnosis?

Dr. Wang:

I think all of them are essential, but in this day and age, for the selection of targeted therapy, it really is the mutational testing, which is looking at the RNA of the tumor cells and determining whether that has been altered in allowing the cells to express abnormal proteins. For standard chemotherapy, we also use DNA testing, which is looking at the different chromosomes and seeing whether there’s breakages or what we call translocations, pieces of chromosomes that have been swapped. That DNA chromosome information can give us some insight into prognosis and therapy response.

So, nowadays, it’s not just determining that you have acute leukemia, but looking at the specific DNA and RNA changes, and I have to say that this is a disease that we’re really not seeing any RNA or mutational changes occurring in more than 20 percent or 30 percent of patients. So all of the mutations that we see that could be impactful really don’t occur in more than 20 percent or 30 percent, and could only occur in five or one percent.

So, really, personalizing an individual patient’s disease, both for the disease biology as well as the person that’s getting the chemotherapy or the diagnosis, is really, really important.

Katherine:

Yeah. Let’s define a few terms that are often confusing for patients. What are biomarkers?

Dr. Wang:

Biomarkers are either proteins or expression levels on the cancer cells that can serve to tell us information about the biology of the disease. Okay, so, for example, if you have evidence of residual tumor proteins in your blood, that could be a marker, for example, of minimal residual disease, okay? And, that can tell you maybe one in a million cells have that biomarker, and then you can tell that those one-in-a-million cells are leukemia cells.

So, they’re any marker that we’re using that’s specific for the tumor that can help us in predicting or finding or locating or determining if a tumor would respond to a certain therapy.

Katherine:

What is biomarker testing?

Dr. Wang:

Biomarker testing can be done in many ways. For example, biomarker testing is drawing a sample from the patient and evaluating a marker that we think is going to predict for the disease type.

So, for example, in some cancers, we don’t want to biopsy the lung mass or the tumor mass every single time to see whether it’s shrinking, or getting smaller, or responding. So, in those patients, sometimes we’ll draw a blood sample, and we’ll look for a surrogate marker – some protein that’s expressed in the blood or some DNA or RNA in the blood that is a surrogate or a marker of the tumor so you don’t have to directly biopsy it.

In acute myeloid leukemia, we are looking for – like I said – particular cells in the blood that have particular proteins, and we measure those rather than going ahead and doing that bone marrow biopsy or biopsying those tumors. So, generally, in leukemia, it involves drawing blood samples – that’s the most common; it is a bloodborne disease.

Sometimes, we actually have to go into the bone marrow and do a bone marrow sample, but those biomarkers, as I said, can really improve our ability to detect very, very low levels of disease. So, for example, using a conventional bone marrow biopsy, we can only really detect 1 out of 200 cancer cells by normal – just by visual looking at, but by measuring biomarkers and mutations and other abnormal proteins, we can improve that to 1 in 100,000 cells.

So, really, these biomarkers are very sensitive and important because we want to detect the disease at a point where it’s very, very low. We don’t want to wait until the disease gets very advanced, in which case we think our therapies are less effective.

Katherine:

What is a genetic mutation?

Dr. Wang:

A genetic mutation is a mutation that occurs in the RNA of a cancer cell. That RNA dam – RNA aberration or abnormality does lead to different RNA – what we call transcript levels that lead to abnormal proteins.

Those proteins function in the cells to make a cell a cancer cell, okay? So, all cancer cells start out as normal cells, and as they acquire a mutation, they become a little less normal, and they start acquiring multiple mutations, and some of these mutations occur without DNA changes, some of them occur with DNA changes. And as these abnormalities occur, the cell gets more and more dysfunctional, and eventually, it starts becoming almost evil-ish.

It starts acquiring behaviors that are not normal, and then it starts to grow out of control, and that unchecked growth really is the end result of potentially many mutations occurring over time to drive that cell into becoming a cancer cell, and we call that process transformation, transforming from a normal, healthy-looking cell into almost a monstrous, cancer-like cell.

Katherine:

How do biomarkers affect AML treatment choices?

Dr. Wang:

So, those biomarkers, as I talked about, those mutations can determine what type of therapy patients can have. For example, up to 25 percent or 37 percent of newly diagnosed AML patients will have leukemia cells that carry the biomarker or the mutation in a gene called FLT3, or “flit.”

Those FLT3 cells can be inhibited by specific targeted therapies, including a drug called gilteritinib (Xospata), which is a pill which blocks mutant FLT3 expressed by AML cells. So, we’ve demonstrated, actually, in a randomized clinical trial that patients who have relapsed or recurrent AML who carry cells that have that biomarker – that FLT3 mutation – will actually do better if they take a daily pill – a FLT3 inhibitor – every single day for treatment of their aggressive acute myeloid leukemia than if we gave them low- or even high-dose chemotherapy in the hospital for four to six weeks.

So, that’s the power of those targeted therapies. Because the biomarker is telling you that there’s a sensitivity of that cancer cell to a specific blockage of that pathway, that can really dramatically change the course.

That is where the importance and the power of those biomarkers really goes into play. In the past, patients who had acute myeloid leukemia with FLT3 mutations did poorly with chemotherapy and had disease that came back even after multiple rounds of that intensive chemotherapy. The fact that we can give a pill and people could do better or even go to a bone marrow transplant off treatment with the pill is pretty remarkable.

Which AML Treatment Is Right for You? What You Need to Know

Which AML Treatment Is Right for You? What You Need to Know from Patient Empowerment Network on Vimeo.

What should you know before deciding which treatment is best for YOUR AML? AML specialist Dr. Ellen Ritchie reviews key factors that guide treatment choices, including biomarker testing results, and shares advice for partnering with your team to advocate for the best care.

Dr. Ellen K. Ritchie is assistant professor of medicine and a member of the Leukemia Program at the Weill Cornell Medical College of Cornell University and the New York Presbyterian Hospital. More about Dr. Ritchie, here: weillcornell.org/ekritchie.

Download Program Resource Guide

See More From INSIST! AML

Related Resources:

Expert Advice for AML Patients When Making Treatment Choices

Transcript:

Katherine:

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to discuss how to access the most personalized AML therapy for your individual disease, and why it’s essential to insist on key testing. Before we meet our guest, let’s review a few important details. The reminder email you received about this program, contains a link to program materials. If you haven’t already, click that link to access information to follow along during this webinar. 

Finally, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. All right, let’s meet our guest today. Joining me is Dr. Ellen Ritchie. Dr. Ritchie, would you please introduce yourself? 

Dr. Ritchie:

Hello, my name is Dr. Ellen Ritchie, and I am an attending with a Leukemia service, and an assistant director since, for the last 15 years. 

And I treat mainly Acute Myeloid Leukemia, Myelodysplastic syndromes, which are kind of a pre-Leukemia; and Myeloproliferative diseases. And have a particular interest in the treatment of older patients with AML.  

Katherine:

Excellent, well thank you so much for joining us today. As we begin to talk about personalized therapy and AML, let’s start with the basics. How would you define personalized medicine? 

Dr. Ritchie:

Personalized medicine, to me is really, it’s a difficult question. It’s trying to find the best treatment for a particular patient. And it’s looking at biologic issues, what kind of cancer, what type of AML is it, what are the specific mutations or chromosomal abnormalities. But it’s also looking at the person. Is the patient active or not active? Do they have lots of other diseases like diabetes and coronary artery disease? Or pulmonary disease, or are they completely healthy? 

Or, do they have support at home? If they’re sick at home is there someone who can take care of them, versus a situation where you’re older and alone and you have no real family member to rely on. So, all of these things are very important in making a personalized decision as to how you treat a patient. 

Katherine:

Well, it sounds like, each person’s AML is unique. So, let’s help our audience be clear about basic testing. What tests are necessary to help understand a patient’s specific disease at diagnosis? 

 Dr. Ritchie:

I mean certainly it’s important to do a physical exam and to find out what the general health of the patient is. In order to evaluate an AML, or any other Leukemia, I look at the peripheral blood smear. To look at what I think the type of Leukemia might be that I am dealing with. There are some Leukemias that have particular way that they look like Acute Promyelocytic Leukemia for which there is a designated therapy which works.  

And you can tell that just by looking at a peripheral blood slide. The next test is always a bone marrow biopsy. Patients are not delighted that that is a test, but it is a test that can be done in the office, usually within 15 to 20 minutes. And that test gives us a lot of information. It gives us information about what type of AML it is, what are the markers on the outside of the cell, it gives us information about the chromosomes inside the Leukemia cell. Are there missing chromosomes, or rearranged chromosomes? And if there are, that can be very relevant to the prognosis. And lastly, it’s sent for a particular mutations or markers. So, we look for IDH3 mutations, we look for FLT3 mutations, we look for IDH1 and IDH2 mutations, and we do an entire myeloid panel. Which is about 44/45 genes that are most commonly mutated in patients with AML.  

So that’s the initial work up for any AML patient. 

Katherine:

You mentioned markers Dr. Ritchie. What is genomic, or bio marker testing? 

Dr. Ritchie:

So, we’re looking really at most specifically at mutations inside individual genes that might be in your Leukemia cell. So, there are some mutations actually that confer a better prognosis. Like NPM1 or CEPBA, those can be more positive type of prognosis than some of the others.  

But we’re also looking for markers that might be targetable with certain therapies that we have. So, if you have a FLT3 ITD or TKD, we actually have particular drugs which can target those particular mutations. There are also drugs that are FDA approved to treat IDH1 and IDH2 mutations. 

There are certain mutations that have a relatively poor prognosis, like TP53 for which there are clinical trials which are available, which specifically are meant to target patients who have those sorts of mutations. And there’re other clinical trials using the FDA approved drugs that I just mentioned, for FLT3, for IDH1 and IDH2 and combining it with other agents to try and improve outcome in AML patients. 

Katherine:

Some patients may not know if they’ve received these important tests, so what key questions should they be asking their physician about testing? 

Dr. Ritchie:

So, physicians, they – financial coverage of the mutational testing is not uniform across the country and across insurances. So, Medicare and different Medicare insurances and some of the private insurances all vary in their coverage.  

So, in my clinic, I am asking – I prefer the test that we do in house at Cornell. But it’s important that I ask, what will their insurance cover. And make sure that I send the appropriate testing that will be covered by insurance. There are some insurances that will not cover this type of testing. So, it is a real question for the patient, when you go to see the doctor to say, are you going to do mutational NGS testing?  

And, will my insurance cover this? Hopefully most – if Medicare adopts the coverage of these types of mutational testing, it’s often true that private insurance will eventually pick this up. But it’s a murky field and it’s really important to talk to your doctor about this. The cost of the bone marrow biopsy, and the chromosomal evaluation is nearly always covered by insurance.  

Katherine:

Okay, that’s really great advice, thank you. How do the results of these tests affect prognosis and treatment? 

Dr. Ritchie:

Well, when a patient has AML, if they are a fit patient, if it will help us determine after initial induction, whether to cure the patient we need to do a bone marrow transplant, or we can just continue with chemotherapy.  

And those are really important things to determine. So, if you have a good prognosis AML, if you have an AML that has certain translocations like inversion 16 or 821, or if you have a CEPBA mutation or you have an NPM1 mutation, and that’s all you have, you may do particularly well with chemotherapy treatment alone. And you won’t need to have a bone marrow transplant. 

If you have certain other mutations, we know that the only way that we’re going to cure you, is with a bone marrow transplant. And if you are fit, when we finish induction and even as we’re doing induction, we’re preparing you for a bone marrow transplant down the line.  

One disadvantage, just to mention about the molecular testing, is it doesn’t come back as quickly as some of the other testing. So that you will have already started induction chemotherapy most generally before the mutational testing comes back. Which can be anywhere – depending upon the institution, between seven and 21 days. So, it takes time for those results to be available.  

Katherine:

Outside of test results Dr. Ritchie, what other factors should be considered when choosing treatment? 

Dr. Ritchie:

So, you want to choose whether a patient is most likely to benefit from intense induction chemotherapy. With strong chemotherapies where the backbone of those therapies would be an anthracycline, like Daunorubicin or Cytarabine, or Daunorubicin or Idarubicin, together with Cytarabine. And these are intensive chemotherapies. Versus, non-intensive chemotherapy which is able to be done as an outpatient, more frequently. And it is something that is gentler for a patient, they’re less likely to have severe toxicity. And the backbone of those regimens is using a drug called Azacitidine or Decitabine, together with a second drug called Venetoclax. 

So, these are the two backbones, there may be clinical trials or there may be targetable aspects of your Leukemia, which drugs would be added to either of those backbones. But those are the two backbones. And I also like to identify those patients that may not benefit from chemotherapy at all. And so, it’s very important, I think to really get to know your patient. And I spend time with my patient, particularly on the first visit, to understand not only their physical health, but their mental health. How good is their cognition, what is their mood, are they depressed, or are they happy people? And what is their circumstance? Do they have people to support them? Do they live close to family? Is a caregiver able to come, with an elderly patient for example, to visits? 

Those, and whether or not they’re living alone and need tremendous support. So that’s really important to determine and helps me to choose what the best therapy might be. And also, concurrently what I can do to shore up the patient to do better with whatever therapy that I’m giving them. I.E., if you’re depressed, let’s work on that, or if your blood pressure is too high, or if you are – your diabetes is out of control at the same time that I’m seeing you, to try and fix those particular problems. In older patients I often do sort of a miniature version of the geriatric assessment. And in trials that have been so far, the most important aspects of the geriatric assessment, are really what is your cognitive function? Do have a mild dementia or do you not have a mild dementia? Because dementia may be or mild dementia may be associated with poorer outcome. 

The other is, are you able to do what we call the incidental tasks of daily life. So, you know fundamental tasks are really brushing your teeth and combing your hair, and dressing yourself. But are you able to do your cooking and your shopping and your banking and those things? Patients who have trouble doing their cooking and shopping and banking, and those types of activities, that also has been associated with a poor overall survival in AML. So, it’s really important to determine all of those aspects and if there are any deficiencies, to really know that the only therapeutic choice for that particular patient would be a low-intensity therapy. 

Katherine:

You touched upon this earlier, but what targeted therapies or treatments are available for AML patients? 

Dr. Ritchie:

So, there have been many recent FDA approvals of drugs that are targeted. One, is the FLT3 inhibitors. And the two that are available are Midostaurin, which is most commonly – was the first drug that was really added to intensive chemotherapy. 

And clinical trials show that in those FLT3 positive population that patients had an overall better outcome if Midostaurin were added to intensive chemotherapy. There’s also a drug called gilteritinib, and this drug is also a FLT3 inhibitor that was tested in patients who had refractory leukemia. They could either get real chemotherapy regimen or they could get gilteritinib. And it turns out in the FLT3-positive patients, the gilteritinib was superior to the strong chemotherapy. So that’s been approved for patients who have refractory, or disease that didn’t really respond to initial therapy, that is IDH – or is FLT3 positive.  

Then there’s the IDH1 and IDH2 inhibitors that have also been approved, and a small proportion of AML patients will be positive for IDH1 or IDH2 mutations. 

The IDH1 inhibitor Ivosidenib, is available and can be used to treat patients if you know up front, they have an IDH1 inhibitor. So, that’s a regimen where the single agent can be used to treat an IDH1 mutated patient who’s newly diagnosed. Those patients are also eligible for many clinical trials now, where they’re combining that particular drug with other agents, in an effort to improve outcome. For IDH2 positive patients, there’s a drug called Enasidenib. And this drug is used mainly in patients in the second line setting. But it specifically targets IDH2. And patients go into remission sometimes for a prolonged period of time. So, these drugs are FDA approved, and they’re treating targetable mutations.  

TP53 mutations are a particularly bothersome mutation because it confers a poor outcome. And I’m happy to say that we have clinical trials now that are available that actually target TP53 mutations.  

So, there are – there is therapy available for that type of mutation that was not available before through the clinical trials. And I expect in coming years that we’re gonna see more and more targeted therapies develop in AML which can be used potentially in combination with what we’re already using as backbones to enhance the outcome of patients with this disease. 

Katherine:

Well, how do targeted therapies work? 

Dr. Ritchie:

So, targeted therapies work on – it’s sort of complicated. The targets which are available, IDH or the FLT3 is really on the outside of the cell and it is a drug which is targeted directly to the FLT3 on the outside of the cell. 

It works quite well in the peripheral blood, where you see the blast oftentimes disappear. The big concern always is how well it’s working getting deep into the marrow. But it’s looking at the target on the outside of the cell. IDH1 and IDH2 inhibitors work on particular chemicals which are involved in the kreb cycle, and those of you that took high school chemistry may have memories buried in the deep parts of your brain of learning the kreb cycle. And this is a fundamental metabolic cycle inside cells, and if you have a mutation, an IDH1 or IDH2, you’re unable to go through that full kreb cycle in the appropriate way. And that is something that leads to you having a cancer, in this case AML. So, these drugs actually interfere with what’s happening in that kreb cycle, and allow you to make more normal cells. 

Katherine:

You mentioned earlier Dr. Ritchie, low-intensity therapy. Could you tell us about the types of treatment options? 

Dr. Ritchie:

So, I’ll go – high-intensity therapy or intense chemotherapy always has to be given really in a hospital. And if you don’t start it – if you can start certain intensive chemotherapies, like Vyxeos, which is also intensive, in the outpatient setting, but by day seven or eight, you end up in the hospital. And in intensive chemotherapies, you lose your hair, there’s GI toxicities, you’re at high risk of developing infections and you need a lot of transfusion. And for even young people, it’s a difficult therapy for which you’re in the hospital, and 90-some percent of patients are on IV antibiotics. 

So, it’s intensive chemotherapy because it has to be given in a hospital setting and requires intensive supportive care. Low-intensity therapy can be given in the outpatient setting. So, at the present time you can get a drug like Azacitidine, for example, which is an injection that you get seven days in a row. Unfortunately, you have to come to the doctor’s office every day for those injections, but once you’ve had the injection, you can go home. Combined with Venetoclax which is an oral agent. So, an oral agent can be given at home. You need close supervision in the physician’s office when you’re on this type of therapy, but you don’t need the constant support that you need if you are getting intensive chemotherapy. So, it can be done, in the comfort really of your home and with your family. You will have to come in and have transfusions potentially as an outpatient, nearly everyone does. And there’s always the risk that you develop a fever and if you do, you have to come into the hospital for IV antibiotics. 

But in general, low-intensity means not so much support needed in a hospitalized setting, and the tolerability of this particular chemotherapy in the outpatient setting.  

Katherine:

Once a patient has begun treatment, how do you monitor whether it’s working? 

Dr. Ritchie:

So, one of the more frustrating things about being an AML patient, is you don’t know right off the bat whether or not that you have gone into remission. So, what happens is you receive the chemotherapy, and the day you start chemotherapy is really day one. And somewhere around day 14, you’re at your lowest point. So, your blood counts are low, and you often feel really terrible, and you really wonder, is this working? But unfortunately, I can’t really tell you. Some institutions do bone marrow biopsies if you have intensive chemotherapy on day 14, or if you’re getting Venetoclax therapy somewhere around day 21 to look and see whether they still see Leukemia cells, but the utility of that is different per institution.  

The real test of whether chemotherapy x`, is at the end of about 28-35 days, are your blood counts coming up, and are you making normal blood cells. Are you making platelets, which are the part of the blood that clots the blood? Or are you making neutrophils, which are the important cells needed to help you fight infection. So, the real proof of a remission, is are your platelets over 100,000? Is your neutrophil count over 1,000? And when we look in the bone marrow around that time, do we see normal cells developing and no Leukemia? 

Katherine:

How often should testing take place? And should patients be retested over time? 

Dr. Ritchie:

So, the bone marrow biopsy is done frequently once you have a diagnosis of Acute Leukemia. So certainly, it’s done upon diagnosis of the disease. 

And as I mentioned earlier in certain institutions, about halfway through your chemotherapy cycle, they’ll do a bone marrow biopsy to see whether or not they see any residual Leukemia cells. That’s not done everywhere, and it’s done differently depending upon institutions sometimes. At the end of the chemotherapy treatment, if you recover your blood counts, we do a bone marrow biopsy to confirm a remission. If by day 35, we haven’t seen that your blood counts are recovering, we may do a bone marrow biopsy to see whether or not we see Leukemia cells in there, or early recovery. So, you’re definitely going to have bone marrows at those time points. If you’ve gone into remission, it depends on what we’d do next as to when you would have another bone marrow biopsy. So, if you’re going to bone marrow transplant you may have one more biopsy, just prior to going into transplant, and another biopsy at the end of the first month after transplant. 

If you’re gonna have what we call ongoing therapy, roughly every three or four months, we may do a bone marrow biopsy to determine whether or not the remission is holding. If during ongoing therapy, we see that there is blood count abnormalities that we weren’t expecting, that might be a reason that we would do a bone marrow biopsy. And that’s unpredictable as to when that would be.  

Katherine:

Dr. Ritchie, what advice do you have for patients to help them feel more confident in speaking up and advocating, being a partner in their care? 

Dr. Ritchie:

Well, when you choose a Leukemia doctor, you need to choose someone that you can actually communicate with. Someone who you feel is not allowing you to ask questions, or is not curious about what your life is like, you may wanna think, I wanna check out somebody else.  

Because it’s really important you like the person who’s your doctor, and that you have a trust relationship together. So, it’s really – I tell some patients it’s a marriage of convenience that we have. And that you really have to think of it that way. If someone doesn’t allow you to ask questions or if they are not fully answering your questions in a way that you understand, try and speak up for yourself and make sure that the doctor tries to address that. And if the doctor won’t address those things for you, or you feel like you don’t understand what is being explained to you, then you can think about trying to see someone else. I think it’s really important if you can, to write down as many questions as you have about your disease before you come in. 

Because often what happens is you get there, you’re stunned by the amount of information, and the questions you wanted to ask, you forget. And the next day, you’re like, ugh, I didn’t ask these questions. So, before you come in, if you write questions. Questions about insurance coverage, that may not be something that we go over. Or questions about toxicities, or questions, if I’m gonna lose my hair, do you have the name of a wig facility. All these questions that you might have, put them on a piece of paper, so that they can be addressed when you’re with the doctor. And other things will come up, you’ll have other questions when you’re there, but make sure your fundamental questions are answered. 

Katherine:

Yeah, those are great suggestions. We have a couple of audience questions. Mike wants to know, what does it mean to have high-risk AML? 

Dr. Ritchie:

High-risk AML means that there is something in your chromosomes that are worrisome and may confer a worse outcome. Or that one of the mutations that you have, or the combination of mutations that you have and the genetic testing are poor risk mutations that are associated with poor outcome. So, high-risk, really means a high risk of progression, or a high risk of – it’s a high risk of not going into remission and not being treatable AML. So, these are AMLs we treat aggressively, and if we get a patient into remission, we generally send high-risk patients to a bone marrow transplant. 

Katherine:

The second question is from Craig, he says; I’m currently undergoing treatment for AML, is the Covid-19 vaccine safe and effective? 

Dr. Ritchie:

I recommend the Covid-19 vaccine to everyone, all my patients. A little immunity is better than none. And there is preliminary data, looking at patients with Myeloid malignancies, not Lymphoid, but Myeloid malignancies, where it appears there is an immune response to the Covid-19 vaccine. So, I would suggest that you get the Covid-19 vaccine. Any of them that are available, are good. Whether it’s Moderna, or Pfizer, or Johnson and Johnson. Whatever is available to you, you should go ahead and get. 

Katherine:

Are there any symptoms or issues that AML patients should be looking for post-vaccine? 

Dr. Ritchie:

Post-vaccine, there’s a lot of symptoms that people have. And they can be similar among Myeloid patients. Some of my patients have had no reaction whatsoever, some people have had a really sore arm. 

Some patients are incredibly tired after the vaccine; some patients develop a low-grade fever for a couple of days. Those are really what we watch for. Sometimes when there’s a reaction, we’re hopeful that there’s an antibody being made, or an immune response that’s developing. So, it’s not always a bad thing if you have a reaction. But I don’t think that the reactions of patients of Myeloid malignancies is any different than that of the general public. 

Katherine:

That’s what it sounds like. To close Dr. Ritchie, what would you like to leave the audience with? Are you hopeful about the future of AML treatment? 

Dr. Ritchie:

I’m very hopeful. I’ve worked in this field for 15 years and through the 15 years we have seen a lot of new drugs that have been approved for AML. It’s remarkable, the FLT3 inhibitors, IDH1 and IDH2 inhibitors, new formulations of intensive chemotherapy, like Vyxeos, the Pfizer drug; glasdegib – I can never say that one. And most importantly, venetoclax, which has really revolutionized our treatment of low-risk, or not low-risk, but the low intensity patient. 

I see in the future that there is gonna be more – there’s an emphasis on immunotherapy, so I think we’re gonna see more antibody-based therapy that’s going to be approved by the FDA. Maybe it will be used in combination with the drugs that we are already using. There are all sorts of combinations using all the FDA approved drugs in different ways together. So, we can maybe do better with the drugs that we have. And there’s always new targeted drugs which are being tested in AML. So, I think as time goes on, from a molecular perspective it will be even more targeted. And I’m hoping also that there will be oral formulations of a lot of our drugs. So, it’s kind of exciting that there’s an oral form of Decitabine called Inqovi, which is something that could potentially be given in induction therapy right off the bat with Venetoclax for an all-oral regimen at home. 

All of these things are great advances, in my opinion, and I think that the opportunity to treat patients outside the hospital, with more targeted therapy and immunotherapy is gonna be the future. 

Katherine:

Yeah. And the future sounds promising. Thank you so much for joining us today Dr. Ritchie. 

Dr. Ritchie:

Thank you for having me. 

Katherine:

And thank you to all of our partners.  

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

Treatment Approaches in AML: Key Testing for Personalized Care

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.

About the Guest:
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: https://faculty.mdanderson.org/profiles/naval_daver.html

Expert Advice for AML Patients When Making Treatment Choices

Expert Advice for AML Patients When Making Treatment Choices from Patient Empowerment Network on Vimeo.

What are key factors to consider for acute myeloid leukemia (AML) patients when making treatment decisions? Dr. David Sallman reviews important considerations and their impact on treatment choices, and shares questions patients should ask their doctor to receive optimal care. 

Dr. David Sallman is an Assistant Member in the Department of Malignant Hematology at Moffitt Cancer Center where he specializes in myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN). Learn more about Dr. Sallman, here.

See More From Engage AML


Related Resources:

 

How Molecular Testing Has Transformed AML Treatment Options


Transcript:

Katherine:

When making a treatment choice, what are three key considerations for AML patients?

Dr. Sallman:

Yeah, so I think the initial probably two main questions are is the patient fit or non-fit, and that’s really an evolving definition. I think historically, we had this magical age if you’re less than 60 or less than 65 years of age, but we’ve really gone past that significantly. So, does a patient have significant medical problems, decreased performance status that we would not think about intensive therapy is one of the main questions. I think what feeds into that. And the other big question is what is the underlying mutations that the patient has which really gives us a prognostic risk from a disease perspective.

With certain mutations and subgroups being much more sensitive to intensive chemotherapy and other groups really where that option is poor irrespective of age. So, I think the most important thing is how does the patient look, what is their fitness level, and what are the underlying cytogenetic and molecular changes that impact their disease.

I think third, of course, is really involving the patient in their preferences, because I think some of these can really be a decision between several options.

Katherine:

What’s the role of the patient in making treatment decisions?

Dr. Sallman:

Yeah, the patient has to be central. I’m really hoping that we’ve moved a long way from the paternalistic practices in the past.

I think there are still many instances where there’s sort of a clear best option from a medical perspective, but there’s a lot of social logistics. If you’re getting intensive therapy, as an example, you’re going to be in the hospital four to five weeks, what’s your support system? What financial, other impact factors, all of these things come into play. I think it’s a tough group. I think the patients that are, let’s say, 60 to 70, because responses are somewhat similar across non-intensive and intensive options, I think there’s the question of is the goal long-term, is the goal quality of life, and I think all of those really are impactful.

I think it can be very challenging to go through all of the specific numbers and how a patient comprehends that or not, but really trying to draw out is their goal long-term, is their goal quality of life, give them the pros and cons of the potential options in that setting, and then real-time discuss that as we go. I think when they have that buy-in from their goals, it’s important.

These are complicated regimens and patient compliance and follow-up and all that are really critical to the overall safety and good outcomes of these patients.

Katherine:

Are there questions that patients should ask in their proposed treatment plan?

Dr. Sallman:

Yeah. I think it’s always important to discuss what options. I think any time there’s a one-option, if there is a one-option, why? Maybe because standard of care in this group is so good that it’s not really reasonable to necessarily offer a main alternative regimen. I think it’s important to understand as much of the disease as possible. If you’re choosing this regimen, why are you doing it? I think asking about the mutations is important, although that’s a very complicated thing to explain. Some patients like it and some patients don’t, and I think you have to do that in your team-based relationship.

I think always asking about clinical trials is an important question to ask. Should they be getting a second opinion? These are overall very rare diseases, and we highly favor an initial consultation at an academic center that specializes in this. I’d say a majority of my patients are ultimately treated in the community. But especially given that the regimens are becoming much more complicated, the intensity of watching their counts, managing side effects, titrating medications, it’s really great to have a team-based model between academic and community centers and that can’t really ever happen if they never come to us. As much as possible for that to occur I think is important as well.

How Molecular Testing Has Transformed AML Treatment Options

How Molecular Testing Has Transformed AML Treatment Options from Patient Empowerment Network on Vimeo.

How has molecular testing impacted approaches to acute myeloid leukemia (AML) therapy? Dr. David Sallman explains how molecular testing has transformed AML care, including a discussion of risk assessment and the role of next-generation sequencing (NGS) in tailoring care for each patient. 

Dr. David Sallman is an Assistant Member in the Department of Malignant Hematology at Moffitt Cancer Center where he specializes in myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN). Learn more about Dr. Sallman, here.

See More From INSIST! AML


Related Resources:

 

Understanding AML Induction and Consolidation Therapy

Transcript:

Katherine:

How has molecular testing changed the landscape of therapy for AML?

Dr. Sallman:

Yeah, it’s really transformed it, and it’s really a constantly evolving paradigm. We have updated classifications; most people utilizing the ELN system.

So, based on both cytogenetic and molecular factors, you can ultimately go into good risk, intermediate risk, adverse risk. In general, for fit patients for good risk, we focus on curative intent, ideally with chemotherapy alone. For intermediate and adverse, typically we’re incorporating allogeneic stem cell transplant. So, that’s one of the main things that really guides treatment really from the beginning and throughout.

Then, I think really where it’s evolving is personalized therapy. So, it’s really not a one-size-fits-all treatment paradigm, it’s you have mutation A, B, you’re this age, this fitness, and we put all those things together to ideally come up with the best treatment plan for the patient.

Katherine:

Is molecular testing standard following an AML diagnosis or is this something that patients should ask for?

Dr. Sallman:

It definitely should be standard and I think the challenge is when you say the word “molecular,” it means lots of things to different people. I think in the community, as targeted medications were first approved, so this was with FLT3 inhibitors, subsequently IDH1 and IDH2 inhibitors, I think people are realizing yes, we have to send these sequencing panels, but there’s a potpourri of choices from a lot of different commercial vendors.

Really the key and one of the main messages we try to get across is you really have to assess for both FLT3 as well as really a comprehensive next-gen sequencing panel in order to cover all of the relevant genes at diagnosis and likely at other time points such as relapsed or refractory disease.

So, there’s no question, it’s standard, although unfortunately, it’s still not uncommon where the comprehensive panels are not sent and you’re left with somewhat not a complete picture for your patients. Since we’re personalizing everything, it’s really quite critical to have these data.

Katherine:

Yeah. How does inhibitor therapy work to treat AML?

Dr. Sallman:

So, you have a gene that turns on and turns off as we go, but with the mutation, it’s basically turned on all the time. Then, you can have targeted pills that basically turn it off. Most commonly this is done, there’s the active

or energy site for these different genes, and so these therapies can really specifically block that. I wouldn’t say that’s the only mechanism. There are IDH1 and IDH2 inhibitors and they’re very specific for those mutations. Each mutation may have a little bit different end biology. In general, you have mutation A, and we’re going to turn it off with drug that inhibits A.

Treatment Advances for Aging AML Patients

Treatment Advances for Aging AML Patients from Patient Empowerment Network on Vimeo.

What are the latest acute myeloid leukemia (AML) treatment advances for elderly patients? Dr. David Sallman shares details about new therapies that he’s excited about and their impact on care for all AML patient groups.

Dr. David Sallman is an Assistant Member in the Department of Malignant Hematology at Moffitt Cancer Center where he specializes in myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN). Learn more about Dr. Sallman, here.

See More From Engage AML

Related Resources:

How Molecular Testing Has Transformed AML Treatment Options


Transcript:

Katherine:

Okay. When it comes to AML research and emerging treatment options, what specifically are you excited about?

Dr. Sallman:

Yeah. So, I think probably the most exciting changes have really been in the overall elderly AML setting, although I think are really broadly impactful across patients.

So, the standard has been hypomethylating agents for a long time. This paradigm has recently changed with the FDA approval and now full approval of venetoclax in combination with hypomethylating agents, but we’re still talking about immediate overall survival of 14 months in the Phase III setting.

There are lots of exciting drugs, and I think this is really where the spectrum of myelodysplastic syndrome and acute myeloid leukemia comes into play.

So, I really think in elderly AML, we’re moving towards more triplet type combinations to really ideally move the field forward. That adds levels of complexity, toxicity from additional therapies, but we’re really hoping to truly move that survival curve even more.

There’s a lot of HMA, doublet, triplet combinations that are exciting and I think that’s really where the field is going.

I think at the same time in the failure setting, particularly, let’s say, in the HMA venetoclax failure setting, there’s really a lack of almost any effective therapies. We’re really hoping that novel cellular and immunotherapies will hold significant promise in this group. There are numerous trials that are being considered in this space, but I’m hopeful for it.

What AML Patients Should Know About the COVID-19 Vaccines

What AML Patients Should Know About the COVID-19 Vaccines from Patient Empowerment Network on Vimeo.

What are some key points for acute myeloid leukemia (AML) patients to understand about the COVID-19 vaccines? Dr. David Sallman shares advice for patients who are considering the COVID-19 vaccine.

Dr. David Sallman is an Assistant Member in the Department of Malignant Hematology at Moffitt Cancer Center where he specializes in myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN). Learn more about Dr. Sallman, here.

See More From Engage AML


Related Resources:

 

Understanding AML Induction and Consolidation Therapy

 


Transcript:

Katherine:

Are the COVID-19 vaccines safe for AML patients, and how does the vaccine affect treatment, if at all?

Dr. Sallman:

Yeah, I think that’s a great question. I think it’s really a rapidly evolving day-by-day update. For example, at our center, we vaccinated a high number of patients and we’re actually in a study trying to understand what their antibody production. So, I think the question is less ‘is it safe or not safe,’ but more is it as effective or worthwhile based on patients that have low blood counts.

I think, in general, if a patient is in remission, either post-therapy or on maintenance-type therapy that has a relatively preserved white count and is it’s very reasonable to utilize it, I think we still have the caveat of is it as effective, of course we don’t know that clearly since all the large trials, these patients weren’t really included. But in general, if you’re not severely leukopenic, we are vaccinating a high percentage of patients that we’re monitoring closely, but anecdotally, we’ve not had significant different adverse events from our perspective.

Essential Testing in AML: How Results Impact Care & Treatment Choices

Essential Testing in AML: How Results Impact Care & Treatment Choices from Patient Empowerment Network on Vimeo.

What tests should follow an AML diagnosis and why? Dr. Hetty Carraway, an AML specialist of Cleveland Clinic, reviews the essential testing for patients with AML and explains how those test results may inform treatment decisions.

Dr. Hetty Carraway is Director of the Leukemia Program at Cleveland Clinic. Dr. Carraway cares for patients with acute leukemia and bone marrow failure states. Learn more about Dr. Carraway, here.

Download Program Resource Guide

See More From INSIST! AML

Related Resources:

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

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

Navigating AML Treatment Decisions

Insist! AML Resource Guide

Transcript:

Katherine:      

Hello, and welcome. I’m Katherine Banwell. Today, we’ll discuss how you can be proactive by insisting on better AML care and personalized treatment options. Joining me is Dr. Hetty Carraway.

Welcome, Dr. Carraway. Would you please introduce yourself?

Dr. Carraway:            

Hi. My name is Dr. Hetty Carraway. I’m one of the physicians at the Cleveland Clinic. I work as the Director of the Leukemia Program, and I spend most of my time caring for patients with acute leukemia and bone marrow failure states.

Katherine:                  

Thank you.  Let’s start with the basics. What essential testing should AML patients undergo following a diagnosis?

Dr. Carraway:            

This is a pretty standard workup for patients that have this diagnosis of acute leukemia.

For most of our patients we always evaluate with a peripheral blood count including a complete blood count with differential, typically a comprehensive metabolic panel, and looking at a test called a uric acid, which looks at the cell turnover and the cellular debris in terms of the burden on the kidney. We often will get a bone marrow biopsy with aspirate for patients, and in the diagnosis of leukemia typically that’s already been done.

There are tests that are sent off of that aspirate called a test for chromosomes, whether it’s comprehensive cytogenetics or FISH, for fluorescence in situ hybridization. We’re often testing using a study called NGS or next generation sequencing looking for specific mutations of genes known to be important in the pathogenesis of leukemia.

Furthermore, we often get a test called flow cytometry from that aspirate looking at the markers on top of the leukemia cells that help us to identify the blast population. So, I would say those by and large are the tests in the bone marrow biopsy that we get, which are innumerable and detailed.

They often take some time to get back, so at the time of the diagnosis patients know that they have a diagnosis of leukemia, but those additional chromosome tests or mutation testing that can take up to two weeks if not longer to get back. And so, it’s important to follow up on that information later on and say, has that testing come back? If so, how does that change any of what the decisions are moving forward?

Katherine:                  

Genetic testing can often be confused with molecular testing. What’s the difference between the two, and why should patients undergo the testing?

Dr. Carraway:            

The chromosome testing and the mutational testing help us to really classify the risk in terms of the leukemia itself, whether or not that leukemia is responsive to chemotherapy alone, or if it means that there’s a higher likelihood of that leukemia not being controlled with leukemia only.

In that setting, we often then move towards transplant for curative intent in addition to the chemotherapy. The reasons to get the information is to really help us better tailor the therapy for each individual patient. That information really does help us guide not only the upfront therapy for some patients but even the long-term therapy. It can be incredibly overwhelming to have too much information at the get-go, so in some senses it’s better to have these pieces as they unfold over time.

For other patients, they want to know what exactly the plan is going to be A to Z from day one. That is of course more challenging now that it just takes time to get this information. I think what they need to know is that we’re working hard to get that information.

As soon as we get it, we don’t hold back. We reveal and share that information and come together to say, this is what this data or information means, and these are some of the choices that we either recommend that you consider, and these are the risks and benefits to those considerations.

Katherine:                  

Let’s look at something that is similar to what you’ve just been talking about. How do test results impact treatment and overall care?

Dr. Carraway:            

They really can. When you asked me how come chromosome or genetic information is different than mutational information, the chromosomes can help us to figure out where patients land in terms of prognosis. That information is different than the mutational testing. Both of those pieces can help us figure that out.

The mutational test, I will tell you, does help us figure out are there targets on the leukemia that allow us to use therapy that’s directed to that mutation. The key example I’ll give is a mutation in a gene called FLT3. That particular mutation has an agent now that is F.D.A. approved called Midostaurin, and so once we know that a leukemia harbors a FLT3 mutation we often add a drug called Midostaurin to the backbone therapy that is used for patients.

Now, that’s important, and now there are more and more genes that when mutated we have novel therapies that direct against that specific tag that’s on the leukemia and helps to improve eradication of the disease or control of the disease if you will.

That’s different than the genetic information when we’re looking at chromosomal changes that may allow us to say in the rare instances of  favorable cytogenetics like a translocation of chromosome 15 and 17 consistent with APL, the treatment for that type of leukemia,  acute promyelocytic leukemia, is very different than what we do for the majority of other leukemias.  

The prognosis for that leukemia is also very different. It helps to tailor the regimens, and it helps to select specific therapy that may be helpful to each individual patient.

Katherine:                  

Dr. Carraway, you just mentioned FLT3. Would you tell us about the common mutations in AML and how these may impact treatment options?

Dr. Carraway:            

There’s a multitude of mutations that we’re now following in patients. The way that we follow them is by doing this next generation sequencing test at the upfront time at diagnosis.

The reason why we’re doing that is because those mutations can regress with therapy, or they can progress where you gain additional mutations that happen as the disease progresses. Even if it’s responding to therapy or as it loses response to therapy and reemerges, it may reemerge with different mutations. As a result of that, it may change what therapy we select. Our ability at this point in being to recommend exactly at what time points we are checking the next generation sequencing we’re still learning right now as to what are the key times to do that testing.

In general, most institutions are doing that next generation sequencing at the time of diagnosis, and then also for some patients before they go to bone marrow transplant and even after bone marrow transplant.

For some of those patients that unfortunately relapse, we’re also making sure to retest the next generation sequencing mutation testing to see are there new mutations that have come about that weren’t there before?

Katherine:                 

I understand there’s something called IDH. 

Dr. Carraway:            

You were also asking about what other mutations besides FLT3 happen in patients with AML. FLT3 is one such mutation. NPM1 is another mutation that often it frequents patients that have AML. Those two mutations happen in about 30 percent of patients with AML. There are other mutations such as DNMT3A, ASXL1, and TET2 that we typically see in patients with MDS or even a pre-leukemia state called CHIP. For other patients, we have mutations that are targetable like IDH1 or IDH2.

Those two mutations happen in probably 10 percent to 15 percent of patients diagnosed with AML. Why are those important? They’re important because we have oral medications that are pills that patients can take. In the relapse setting for many patients after induction or intensive chemotherapy, they can use these oral therapies to try and control their leukemia. These are pretty exciting. 

All of these oral therapies have been approved in the last two to three years in the space of leukemia, so it’s been a game-changer in terms of identifying these mutations and then identifying drugs that target those mutations. It’s really changed the landscape for patients with AML. It’s new information, and that’s why as patients you want to hear about this so you know what questions to ask and you know, can you tell me, am I a candidate for one of these oral medications that is now available for patients with AML?

Katherine:                  

Dr. Carraway, thanks so much for joining us today.

Dr. Carraway:            

Thank you for the opportunity to be here. 

Katherine:                  

And thank you to our audience. I’m Katherine Banwell.

Navigating AML Treatment Decisions

Navigating AML Treatment Decisions from Patient Empowerment Network on Vimeo.

What factors can help determine the best treatment path for your AML? This animated video walks through important considerations that may help in navigating treatment decisions, including how genetic testing results, treatment goals and patient preference can impact your choice.

See More From INSIST! AML

Related Resources:

Genetic Mutations That Affect AML Prognosis and Treatment

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

Effective AML Combination Treatment

Transcript:

Hi, I’m Gina. I’m a nurse practitioner and I specialize in acute myeloid leukemia, or AML.

When diagnosed with AML, it’s important to take steps to get a deeper understanding of your disease, and the available treatment options, so that you can feel confident in your care decisions.

Before we walk through the important steps to decide on a treatment path, I want to remind you that this video is intended to help educate AML patients and their loved ones and shouldn’t be a replacement for advice from your doctor.

OK, let’s get started.

The first step is to understand your diagnosis, so that you can find out what treatments are available to you. Unlike solid tumor cancers, such as lung or breast cancer, AML is not staged. Instead, your physician will use lab testing, including blood and bone marrow tests, to determine the subtype of your AML and if you have any chromosomal abnormalities to determine if your AML is low, intermediate or high-risk.

Knowing your risk can impact your prognosis and help establish the best treatment option for you. If you don’t know your subtype, ask your doctor for the information and if you may need further testing to reach a more accurate diagnosis.

Testing that identifies characteristics unique to YOUR AML can impact your treatment options and determine if a targeted therapy or immunotherapy might be more effective. These tests include:

  • Molecular testing
  • Cytogenetic analysis (or karyotyping), and
  • Fluorescence in situ hybridization also known as a FISH test

Before you start any treatment, it’s essential to insist that you have had relevant testing.

Next, you should understand treatment goals. The first goal of AML therapy is to get into remission. The second goal is to maintain that remission.

Induction therapy, or the first phase of treatment, is meant to induce remission. This first-line treatment kills as much of the disease as possible and returns blood counts back to normal.

Consolidation treatment, also referred to as post-remission therapy, is used to prevent leukemia cells from returning and maintain remission. In some patients, stem cell transplant acts as a consolidation therapy. In others, additional treatment options to maintain remission can be explored.

The next step is to consider your treatment options with your doctor. It’s important to understand the approaches available for YOUR individual disease. AML treatments can include:

  • Chemotherapy
  • Targeted therapy
  • Stem cell transplant
  • Immunotherapy
  • Clinical trials, which may provide access to treatments that are not yet approved.

Or, you may receive a combination of one or more of these treatments.

Once you understand the therapies that are available to you, it’s time to talk to your doctor about the risks and benefits of each option. Your doctor will also consider your age, overall health, and existing conditions before suggesting a treatment course.

So, what questions should you address when discussing your treatment goals with your doctor? Consider asking:

  • Is stem cell transplant a viable option for you?
  • Can you tolerate high-intensity therapy or is low-intensity therapy better for you?
  • How will the treatment impact your quality of life and lifestyle?
  • Are there short or long-term treatment side effects that may occur after you have completed treatment?
  • What is the plan if the first approach to treatment isn’t effective?
  • Is there a clinical trial that might be right for you?
  • Is there a member of the team, such as a social worker, that can help you understand the potential treatment costs? And is there access to financial resources that can help you if needed?

Remember that you have a role in making decisions regarding your care. Insist that all of your questions are answered when making a decision with your healthcare team. If you don’t feel supported or you don’t feel heard by your healthcare team, then it is always best to seek a second opinion.

Finally, once you have gathered all the information, it may be helpful to talk it out with people you trust, such as a partner, friend or family member, to help you make a decision that you feel confident about.

Now, how can you put this information to work for you?

  • Ensure that you have an accurate understanding of your diagnosis.
  • Make sure you have had appropriate testing to establish your subtype and risk.
  • Understand your treatment options and talk with your doctor about what’s best for YOUR AML.
  • Remember, you are a partner in your care and have an active voice in finding the best treatment for you.

Visit powerfulpatients.org/aml to learn more about AML.

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?