AML Testing Archives

Testing is an ever-present part of the cancer journey, helping identify stage, treatment options, progress, and potential recurrence. Testing can also introduce a whole new vocabulary into your life. Don’t let jargon overwhelm you or undermine your grasp of test options and results.

We can help you evolve into an informed AML advocate who understands results and how to use testing as a conduit to the most personalized care.

More resources for Acute Myeloid Leukemia (AML) Testing from Patient Empowerment Network.

AML Targeted Therapy: How Molecular Test Results Impact Treatment Options

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AML Targeted Therapy: How Molecular Test Results Impact Treatment Options from Patient Empowerment Network on Vimeo.

How could the results of molecular testing affect your acute myeloid leukemia (AML) treatment choice? Dr. Sanam Loghavi explains how inhibitor therapy works to treat AML.

Dr. Sanam Loghavi is a hematopathologist and molecular pathologist at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Loghavi.

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Transcript:

Katherine Banwell:

Dr. Loghavi, how do molecular test results impact the care plan and treatment choices? 

Dr. Sanam Loghavi:

Sure. So, again, associated with really two major factors in the care of the patient. One is the decision of how intensely to treat the patient and whether or not the patient is a candidate for a hematopoietic stem cell transplant. And then the other is the availability of targeted therapies to those patients.  

So, there are now several molecular alterations that make the disease amenable to treatment with targeted therapies, including mutations in FLT3, which is a name of a gene, mutations in IDH1, IDH1 or IDH2. And again, depending on the change, the patients may receive targeted therapy. 

Katherine Banwell:

Dr. Loghavi, you mentioned inhibitor therapy. What is this treatment, and how does it work? 

Dr. Sanam Loghavi:

Sure. So, again, it depends on the medication and it depends on the molecular change. 

But essentially what happens when you have a mutation in a gene the normal function of that gene is impaired and a lot of the times that’s why you develop leukemia is because of the impairment of that normal function. So, usually what targeted therapies do, if that mutation is causing an apparent activation of let’s say a signaling molecule, then those targeted therapies will block that signaling. Or if it’s a deregulation of an epigenetic – and epigenetic means beyond genetic, so epigenetic factor, then the goal of that targeted therapy is to maintain that normal function or restore that normal function. 

Expert Advice for Navigating AML Treatment and Care Decisions Resource Guide

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Does Maintenance Therapy Have a Role in AML Care?

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Does Maintenance Therapy Have a Role in AML Care? from Patient Empowerment Network on Vimeo.

Acute myeloid leukemia (AML) expert Dr. Farhad Ravandi-Kashani discusses the role of new and developing maintenance therapies that may improve remission and how this treatment phase may fit into the future of AML care.

Dr. Farhad Ravandi-Kashani is professor of medicine and Chief of the Section of Developmental Therapeutics in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, TX. Learn more about Dr. Ravandi-Kashani.

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 Advances in AML Research _ Where Do Clinical Trials Fit In

Transcript:

Laura Beth:

Dr. Ravandi, does maintenance therapy have a role in AML?  

Dr. Ravandi:

Maintenance therapy is something that has been used in other leukemias for a long time, and other types of cancer, particularly in ontological cancers. In AML, it hasn’t been normal practice, traditionally, mainly because in AML, we haven’t had many good relatively nontoxic, easily taken drugs.  

So, about 30 years ago, some groups, for example, a German group actually tried to do maintenance with cycles of chemotherapy, and you can imagine if a patient is in remission, and somebody says to you, “I’m going to give you cycles of chemotherapy for the next three years,” most patients wouldn’t take it because they say, “Well, you know, maybe I have three years to live. I want to go to Bahamas and be on the beach rather than getting cycles of chemotherapy.” But over the last several years, in a number of effective, highly effective oral agents that have been developed, and one specific agent that has been developed for maintenance. Now, this specific agent is not curative, as it’s not that if you take it, you will live forever.  

But it does improve survival, and it’s relatively well-tolerated. And there are other clinical trials of maintenance. Agents are being developed, and I think it’s a very important area in AML. And I think in the next several years, it will actually become common practice to do maintenance regimens.  

Laura Beth:

That’s good news. So, once an AML patient is in remission how are they monitored? 

Dr. Ravandi:

So, I mean, I usually tell my patients that once you’re in remission, you’re in remission until something goes wrong with your blood counts. So, in my opinion, it’s not important to do – definitely not important to do weekly blood counts, for example.  

Depending on patient’s anxiety levels and comfort, we do check their labs maybe once a month, once every two or three months, depending on how far they are from their remission. And in my opinion, routine bone marrows are not necessary during remission, unless the patient is a part of a clinical trial that they have accepted to participated in, because we do get a lot of information by doing those bone marrows. So, some studies have follow-up bone marrows, but that’s really as a part of a clinical trial and to help further the knowledge in therapy.  

Advances in AML Research | Where Do Clinical Trials Fit In?

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Advances in AML Research | Where Do Clinical Trials Fit In? from Patient Empowerment Network on Vimeo.

How do clinical trials advance acute myeloid leukemia (AML) research? Dr. Farhad Ravandi-Kashani discusses newer AML treatments that have changed the landscape of care and how patient trial participation moves research forward.

Dr. Farhad Ravandi-Kashani is professor of medicine and Chief of the Section of Developmental Therapeutics in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, TX. Learn more about Dr. Ravandi-Kashani.

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 Does Maintenance Therapy Have a Role in AML Care

Transcript:

Laura Beth:

When it comes to AML research and emerging treatment options, what are you excited about right now?  

Dr. Ravandi:

Well, I think one of the biggest, I would call, revolutionary changes in AML was the introduction of venetoclax (Venclexta), because AML is a disease of the older population.  

The median age is about 68, which means half of the patients are older than 68, and among the other half, majority are older than 55. And when you go beyond 60, 65, traditional chemotherapy is not well-tolerated. But the introduction of venetoclax plus azacitidine (Onureg) or decitabine (Dacogen), depending on the center, has really completely changed the management of older AML patients from a situation that it was dismal treatment to a situation that’s still not great, but it’s a lot better, as in we don’t cure the majority, but many people have a tolerable therapy and live with their disease for several months if not several years.  

And personally, I have treated a 97-year-old patient, and she did well for three years, so. Because of this drug, age is no longer as frightening as it used to be for advanced age. 

Laura Beth:

So, where do clinical trials fit in when it comes to choosing treatment?   

Dr. Ravandi:

So, the best drugs that we have available now, the venetoclax that I mentioned and all the other drugs that I mentioned, targeted drugs, came from clinical trials.  

If we don’t do clinical trials, we would be still doing the same treatments that we were doing in the 1970s and ‘80s.  

In fact, up until about seven or eight years ago, many places were still doing the same treatments that was developed in 1970s, which in the era of computers, and Apple, and everything else, it’s mindboggling that we should be doing something that we were doing in the ‘70s. So, clinical trials are important to move the field forward. They are at major academic centers, all the clinical trials are extremely well-vetted and scientifically vetted, as well as with institutional review boards, ethically vetted. So, patients can be sure that they’re not going to get anything less and potentially more than what they would normally get.  

How Does the Presence of Molecular Markers Affect AML Care?

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How Does the Presence of Molecular Markers Affect AML Care? from Patient Empowerment Network on Vimeo.

Dr. Farhad Ravandi-Kashani reviews how the presence of gene mutations can influence acute myeloid leukemia (AML) treatment choices and discusses new molecular markers being researched for future AML care.

Dr. Farhad Ravandi-Kashani is professor of medicine and Chief of the Section of Developmental Therapeutics in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, TX. Learn more about Dr. Ravandi-Kashani.

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 Does Maintenance Therapy Have a Role in AML Care

Transcript:

Laura Beth:

How do test results impact AML care and treatment decisions?  

Dr. Ravandi:

So, in the first place, the presence or absence of certain mutations can be predictable outcome. Some subsets of leukemias are, for the lack of a better term, more favorable.  

I personally don’t think there is anything favorable about any leukemia, but some are easier to treat, and some are easier to cure than others. There is one specific subtype called acute promyelocytic leukemia that we actually completely treat differently. We don’t use even chemotherapy in that subset of leukemia.  

It has almost 100 percent success rate. And the treatment of other subsets can also be tailored, depending on these molecular and chromosomal changes. So, the initial therapy can be actually changed. There are now, for example, targeted agents that can be added to the chemotherapy, during initial chemotherapy.  

And also, once the patient is in remission, depending on favorable or unfavorable their leukemia is, they may be offered allogeneic stem cell transplant. So, yes, this information is highly important. In fact, I would say crucial for our decision-making in leukemia therapy these days.  

Laura Beth:

So, what is new in AML research related to molecular markers?  

Dr. Ravandi:

Well, it depends on your definition of new, but FLT3 mutations are very important because they’re now several FLT3 inhibitors, and as I mentioned, the initial therapies are different, to some extent. The IDH mutations are very important, again, because they are specific targeted agents.  

TP53 mutations are important because, unfortunately, they are particularly unfavorable.  

This is completely hot off the press, but there are subsets of AML called MLL rearranged leukemias that can respond to these drugs called Menin inhibitors.  

There are other mutations that have been discovered, many other ones, that there are no specific treatments for at the moment, but there’s a lot of research on.  

Diagnosing and Treating AML: What Testing Is Essential?

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Diagnosing and Treating AML: What Testing Is Essential? from Patient Empowerment Network on Vimeo.

How do test results affect the diagnosis and care of patients with acute myeloid leukemia (AML)? Dr. Farhad Ravandi-Kashani reviews essential testing for AML patients, including molecular testing and what these test results might reveal about the disease.

Dr. Farhad Ravandi-Kashani is professor of medicine and Chief of the Section of Developmental Therapeutics in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, TX. Learn more about Dr. Ravandi-Kashani.

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Transcript:

Laura Beth:

Dr. Ravandi, can you define molecular testing for AML patients?  

Dr. Ravandi:

We have progressed on our understanding of cancer, in general. And we have progressed in our technology, so we know that various cancers are likely caused by a number of molecular events, and this is best characterized in leukemias because we have been doing this in leukemia for many years now, simply because leukemias are much more accessible than other cancers. Leukemic cells are in blood and easily obtained and even in bone marrow, are much easier obtained than other solid tumor cancers.  

And so, we’ve been able to identify a number of gene and chromosome changes that we have discovered to be prognostic, but also, have become the targets for developing effective drugs.  

Laura Beth:

Beyond molecular testing, what other testing should take place following an AML diagnosis?  

Dr. Ravandi:

I mean, the classical patient presents because there is something in their blood counts, so they usually have had a blood count testing done. And, of course, you need to do a number of other tests, for example, the chemistry profile, because that can show us some of the problems that can be caused by leukemia.  

And the most important thing is bone marrow aspiration and biopsy, which is still, unfortunately, absolutely necessary, first to make the diagnosis, and second, to obtain the specimens for those biomarker testing that you mentioned.  

Laura Beth:

If a patient relapses, does all of this testing need to be repeated?  

Dr. Ravandi:

Unfortunately, yes. And so, when you said all of these testing, actually, again, compared to some other cancers, this is limited testing. Taking blood for the blood tests, and even doing a bone marrow is generally much easier than taking tissue in a colonoscopy for a colon cancer, or doing a biopsy, a lung biopsy in lung cancer, etc.  

But yes, they all need to be tested, and actually, we do like to repeat the genetic testing because leukemias are dynamic, and after initial therapy, they may change in ways. They may develop new targets or new molecular changes that may be potentially amenable to new targeted therapies.  

Laura Beth:

And is it common for a mutation to appear at a relapse?  

Dr. Ravandi:

It is, yes. I mean, I would say it’s – I wouldn’t say it’s common, but it is frequent.  

How Do Gene Mutations Affect AML Treatment Choices?

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How Do Gene Mutations Affect AML Treatment Choices? from Patient Empowerment Network on Vimeo.

Dr. Eytan Stein shares why AML patients should undergo molecular testing when choosing a treatment approach, explaining how targeted therapy works to treat AML patients who have specific genetic mutations.

Dr. Eytan Stein is a hematologist oncologist at Memorial Sloan Kettering Cancer Center and serves as Director of the Program for Drug Development in Leukemia in Division of Hematologic Malignancies. Learn more about Dr. Stein, here.

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Transcript:

Katherine Banwell:

Why is identification of genetic markers essential before choosing treatment?  

Dr. Eytan Stein:

Because when you know the genetic markers, you can target the genetic abnormalities, sometimes with specific targeted therapies, with therapies that fit like a key in a specific lock.  

And those targeted therapies have been shown, in some cases, to improve the survival of the patients, without much cost, without much toxicity. So, I’ll give you an example of this.  

There is a very common genetic abnormality in patients with acute myeloid leukemia called the FLT3 or FLT3 mutation. When you have that mutation, there is a targeted therapy that targets the FLT3 mutation called midostaurin (Rydapt), and it’s been shown in a very large clinical trial that the addition of the targeted FLT3 inhibitor midostaurin in combination with chemotherapy leads to better overall survival than chemotherapy alone.  

So, you need to know that information because you want to give your patient the best chance at beating the disease. And that’s why it’s also important to try to get this information back quickly. You know, no one wants to be sitting around waiting for four weeks to find out if they’ve got a specific mutation. And we’ve gotten better. I think medical centers generally have gotten better at getting this mutational information back to their doctors relatively quickly. 

Katherine Banwell:

Does every patient get this standard testing? 

Dr. Eytan Stein:

It is – does everyone get it? I don’t know. But “Should everyone get it?” is, I think, the important question. Yes, everyone should get this testing.  

It is incorporated into the NCCN and National Comprehensive Cancer Network and European Leukemia Net guidelines. It is important not only because you can think about targeted therapies, but it is also important for prognostic reasons, meaning that certain mutations lead to a higher risk of relapse, and those mutations in a patient might lead me to recommend a stem cell transplant, which is sort of the most intensive thing we can do to help prevent a relapse, while other mutations, which might be “favorable”, in quotes, they might lead me not to recommend a stem cell transplant.  

So, I think this mutational testing is the standard of care and should be done in every patient with newly diagnosed acute myeloid leukemia.  

Which Tests Do You Need Before Deciding on an AML Treatment Path?

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Which Tests Do You Need Before Deciding on an AML Treatment Path? from Patient Empowerment Network on Vimeo.

 Why is it important to ask about biomarker testing for your AML? Find out how test results could reveal more about your AML and may help determine the most effective treatment approach for your individual disease.

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Transcript:

Why do you need biomarker testing before deciding on a treatment plan for your acute myeloid leukemia—also known as AML?

The results may predict how your AML will behave and could indicate that one type of treatment may be more effective than another.

Biomarker testing—also referred to as risk stratification, genetic testing, or molecular testing—identifies specific gene mutations, proteins, chromosomal abnormalities and/or other molecular changes that are unique to your AML.

The results of these tests are used to determine if you have low-risk or high-risk AML to help guide prognosis and to evaluate the goals of treatment.

There are certain biomarkers—such as the FLT3, IDH1 and IDH2 mutations—that could indicate that your AML may respond well to a targeted therapy. There are several FDA-approved targeted therapies—known as inhibitor therapies—which treat patients with these mutations.

Additionally, the identification of other biomarkers—such as TP53, NPM1, or CEBPA mutations, to name a few—may aid in assessing your prognosis, determining a treatment course, or may identify if an allogeneic stem cell transplant may be appropriate. Results of these tests may also suggest that a clinical trial is your best treatment option.

So, how can you Insist on the best care for YOUR AML?

• First, always bring a friend or a loved one to your appointments to help you process information and to take notes.

• Ask your doctor if you have had, or will receive, biomarker testing and how the results may impact your care and treatment plan. Be sure to ask for paper or electronic copies of your important test results.

• Finally, always speak up and ask questions. It’s important that you understand all of the information that you want to know about your AML to help make the best treatment decisions for you. You are your own best advocate, and treating AML is a team approach.

To learn more about your AML and to access tools for self-advocacy, visit powerfulpatients.org/AML. 

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How Is AML Treatment Effectiveness Monitored?

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How Is AML Treatment Effectiveness Monitored? from Patient Empowerment Network on Vimeo.

How can acute myeloid leukemia (AML) treatment effectiveness be monitored over time? Expert Dr. Ellen Ritchie explains when testing is typically done following AML treatment, which methods are used for monitoring, and when retesting may be appropriate.

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.

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Transcript:

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 (Venclexta) 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 going to 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.

Is the COVID-19 Vaccine Safe and Effective for AML Patients?

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Is the COVID-19 Vaccine Safe and Effective for AML Patients? from Patient Empowerment Network on Vimeo.

What should acute myeloid leukemia (AML) patients know about COVID-19 vaccines? Expert Dr. Ellen Ritchie shares information about COVID-19 vaccine safety and effectiveness for AML patients and reviews side effects that may follow vaccination.

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.

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Transcript:

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 & 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.

How to Be a Partner in Your AML Care

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How to Be a Partner in Your AML Care from Patient Empowerment Network on Vimeo.

How can acute myeloid leukemia (AML) patients take a proactive approach to their care? Expert Dr. Ellen Ritchie shares advice for qualities to look for in your AML care provider and how to ensure all your questions are answered by your healthcare team.

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.

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Transcript:

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 want to think, I want to 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 going to 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.

What Is Low-Intensity AML Therapy?

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What Is Low-Intensity AML Therapy? from Patient Empowerment Network on Vimeo.

How does low-intensity AML therapy differ from high-intensity AML therapy? Expert Dr. Ellen Ritchie provides a comparison of the administration methods, side effects and reviews which AML patients low-intensity and high-intensity therapy are right for.

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.

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Transcript:

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 daunorubicin and cytarabine (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 (Vidaza), 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 (Venclexta) 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.

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

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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.

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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.