ACUTE MYELOID LEUKEMIA (AML) Archives

Acute myeloid leukemia (AML) is a fast-growing form of cancer of the blood and bone marrow. AML is the most common type of acute leukemia and occurs when the bone marrow begins to make blasts, cells that have not yet completely matured. These blasts normally develop into white blood cells, but AML, these cells do not develop and are unable to ward off infections.

In AML, the bone marrow may also make abnormal red blood cells and platelets. The number of these abnormal cells increases rapidly, and the abnormal cells begin to crowd out the normal white blood cells, red blood cells and platelets that the body needs.

Long-Term Effects Acute Myeloid Leukemia Patients Should Know

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Long-Term Effects Acute Myeloid Leukemia Patients Should Know from Patient Empowerment Network on Vimeo.

What do acute myeloid leukemia (AML) need to know about potential long-term effects of treatment? Dr. Catherine Lai from Penn Medicine shares insight. Learn about medical considerations for monitoring and an activation tip to help patients ensure their optimal health for the long term.

[ACT]IVATION TIP from Dr. Lai: “Make sure that you’re reporting all your symptoms, however small that they may be at your appointment, so it can be discussed in asking if it might be related to a late effect, and then also asking if there is a survivorship clinic or a program that you can be a part of.”

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AML Clinical Trials Critical to Treatment Breakthroughs and Improvements

Transcript: 

Art:

Dr. Lai, I was diagnosed with lots more than 20 years after my transplant, and there are the long-term effects that AML patients should be aware of. What are some of those effects?

Dr. Catherine Lai:

Yeah, so that’s an extremely important question and one that is often, often overlooked, unfortunately, even just from a time constraint perspective, but I would say it depends on the type of chemotherapy and the type of transplant, whether it was myeloablative you received radiation before your transplant, but, in general, I mean things to consider or just think about, it’s a big work, and so about your heart, your lungs, your thyroid, your kidneys, and also age-appropriate cancer screening as all things that need to be taken into consideration as late effects, if you are able to…if you’re able to find a cancer center with a survivorship clinic, I think that that’s an extremely valuable resource, because not only are they able to address these medical issues, but they’re also able to address the psychosocial component as well, and just overall general well-being.

And so I think just being aware of the fact that there are late effects and the activation tip being, is that to make sure that you’re reporting all your symptoms, however small that they may be at your appointment, so it can be discussed in asking if it might be related to a late effect, and then also asking if there is a survivorship clinic or a program that you can be a part of.  

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What Are Some Clinical Predictors for Relapse in Acute Myeloid Leukemia?

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What Are Some Clinical Predictors for Relapse in Acute Myeloid Leukemia? from Patient Empowerment Network on Vimeo.

What do acute myeloid leukemia (AML) patients need to know about risk of relapse? Dr. Catherine Lai from Penn Medicine explains her perspective. Learn about relapse risk groups and testing that may help in determining risk of relapse. 

[ACT]IVATION TIP from Dr. Lai: “Have a conversation with your provider about mutations, and do you as a patient have a specific mutation that can be…that can be tracked and also specifically what risk group on my end, what risk group am I in, because that also gives some insight as to your risk of relapse.”

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Long-Term Effects Acute Myeloid Leukemia Patients Should Know

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 What Is FLT3-Mutated Acute Myeloid Leukemia

What Is FLT3-Mutated Acute Myeloid Leukemia?

Transcript: 

Art:

Dr. Lai, what are some of the clinical predictors for relapse in AML patients?

Dr. Catherine Lai:

So, in general, predictors of relapse, some of it depends on what risk category you’re in, so whether or not you’re favorable, intermediate, or adverse risk of the adverse risk patients are more likely to relapse once in complete remission. The other thing, what I would say is that which mutations are present, a diagnosis is a good…also a good way to track and follow disease.

So if you have a specific mutation is to be able to follow that and to be able to quantify it on testing, and then be able to track to see if that increases over time as a predictor of relapse, I would say that, in general, minimal residual disease testing and these predictors or other blood-based markers are not standards.

So a lot of this is novel and is still not standard of care yet, so the activation to here is to just have a conversation with your provider about mutations, and do you as a patient have a specific mutation that can be…that can be tracked and also specifically what risk group on my end, what risk group am I in, because that also gives some insight as to your risk of relapse. 

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What Are the ASH 2022 Takeaways for AML Patients?

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What Are the ASH 2022 Takeaways for AML Patients? from Patient Empowerment Network on Vimeo.

What do acute myeloid leukemia (AML) patients need to know about ASH 2022 updates? Dr. Catherine Lai from Penn Medicine discusses updates presented at the conference. Learn about combination treatments and a study that examined the use of chemotherapy before transplant. 

[ACT]IVATION TIP from Dr. Lai: “There are a lot of new, exciting therapies that are coming out, and that it’s really novel sequencing strategies and combinations that I think will be the future of AML.”

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Transcript: 

Art:

Dr. Lai, I had a transplant almost 30 years ago for relapsed AML and was not given intensive chemotherapy to get me into remission before the transplant. What are the takeaways from the ASH 2022 meeting? Is less more when treating AML?

Dr. Catherine Lai:

Sorry, that’s a great question, and what I just like to say that it’s so great that you are doing so well, so many years after, as you know, transplant is the original form of immunotherapy and is still the only potential cure for AML. And so with that being said, with at ASH what was seen was, I think a handful of things, so what I would say is that different combinations of drugs being used, so things looking at either at novel doubles and or triplets. Meaning combinations of two or three different drugs and how toxicity is affected, there are other also novel immunotherapies that are out there, not have been as groundbreaking as transplant, and I think that there is some way to harness the immune system to make treatment more effective, we just haven’t found that. Right, chemotherapy.

And then specifically, there was a large study, a large European study that was presented as the plenary session at ASH that talked about the role of chemotherapy before transplant. And what I would say, just speaking in general, is that the new immune system that a patient gets when they get a transplant takes…the new immune system, when a patient gets a transplant, it takes some time to take over, and that new immune system is able to fight off the leukemia, and so if a patient has a slow-growing leukemia, they might not need as much chemotherapy before the transplant, because the rate at which the leukemia will grow and won’t overburden the body before the new immune system takes over.

So I think that study was very provocative and gave some insight, but I still don’t think we have the complete right answer as to what chemotherapy should be used before transplant, I think that’s really tailored to each individual patient.

And then whether or not patients need chemotherapy after transplant also depends on disease burden and status, and taking into account measurable residual disease as well. So I would say the activation tip from the ASH 2022 meeting was that there are a lot of new, exciting therapies that are coming out, and that it’s really novel sequencing strategies and combinations that I think will be the future of AML.

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What Does Transfusion Burden Mean in Acute Myeloid Leukemia?

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What Does Transfusion Burden Mean in Acute Myeloid Leukemia? from Patient Empowerment Network on Vimeo.

What do acute myeloid leukemia (AML) patients need to know about transfusion burden? Dr. Catherine Lai from Penn Medicine explains transfusion burden for AML patients. Learn about the range of transfusion burden and advice from an expert. 

[ACT]IVATION TIP from Dr. Lai: “Discuss how frequently transfusions are needed and how long you may be able to go without needing a blood or platelet transfusion with your physician.“

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A Look at Treatment Strategies for High-Risk AML Patients

Transcript: 

Art:

Dr. Lai, what does transfusion burden mean in AML?

Dr. Catherine Lai:

Yeah, so transfusion burden is the amount of either patients’ blood that you have to receive and or platelets that you have to receive.

So when we say that somebody is transfusion-dependent, that means that they on their weekly blood checks or having to receive transfusions multiple times, whether it be twice a week or once a week, but somebody who cannot make enough blood and our platelets on their own to stay within a safe range and that they need to receive transfusions. 

Typically. now, this is again specific for an individual patient, but in general, most centers use parameters such as the hemoglobin less than 7, in which they get transfused red blood cells and a platelet count less than 10,000 for platelet counts, assuming that patients are feeling well and are healthy and they’re not bleeding.

So here the activation tip would be to discuss how frequently transfusions are needed and how long you may be able to go without needing a blood or platelet transfusion with your physician.  

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Assessing Untreated AML Patients Who Are Ineligible for Intensive Chemotherapy

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Assessing Untreated AML Patients Who Are Ineligible for Intensive Chemotherapy from Patient Empowerment Network on Vimeo.

How are acute myeloid leukemia (AML) patients assessed for intensive chemotherapy? Dr. Catherine Lai from Penn Medicine explains eligibility criteria. Learn factors that impact patient eligibility and treatment options for AML patients who are categorized as ineligible for intensive chemotherapy.

[ACT]IVATION TIP from Dr. Lai: “Talk with your physician about how they will determine whether or not you are fit or unfit for intensive chemotherapy.“

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Transcript: 

Art:

Okay, Dr. Lai, what are we learning about patients with untreated AML who are ineligible for intensive chemotherapy?

Dr. Catherine Lai:

To define ineligible for intensive chemotherapy, I think that that is a moving target because historically, we would define patients as eligible for intensive or less intensive chemotherapy based on an age cut-off. And as the population is becoming more fit and is also getting older, what I would like to say is that we should use physiologic age, not chronologic age to determine who is eligible for intensive chemotherapy, and that is…in terms of how that is assessed, that is not uniformly done. 

But, in general, it takes into account how active a patient is and what they’re able to do on a day-to-day basis, so mostly their physical function, we also take into consideration their cognitive function as well, but to a lesser extent.

So, for patients who are ineligible for intensive chemotherapy, the standard practice would be the combination of azacitidine (Onureg or Vidaza) or decitabine (Dacogen), both of which are hypomethylating agents in combination with venetoclax (Venclexta), and that combination has really changed the landscape in terms of how we treat patients, it can be given as an outpatient, so it’s much better tolerated and has fewer side effects compared to intensive chemotherapy.

So the activation tip here is to talk with your physician about how they will determine whether or not you are fit or unfit for intensive chemotherapy. 

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What AML Treatment Options Are Available for MRD-Positive Patients?

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What AML Treatment Options Are Available for MRD-Positive Patients? from Patient Empowerment Network on Vimeo.

For acute myeloid leukemia (AML) patients who are MRD-positive, what treatment options are available? Dr. Catherine Lai from Penn Medicine discusses MRD-positive concerns. Learn about recent guideline updates for MRD-positive and genetically adverse patients and key questions to ask your care provider. 

[ACT]IVATION TIP from Dr. Lai: “For genetically adverse risk, it would be to have a conversation about whether or not you should be going to transplant. And for MRD-positive patients, I would say is to ask about how frequently my testing should be done to monitor for MRD, MRD-positive disease.“

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What Are the Latest Acute Myeloid Leukemia Therapies?

Transcript: 

Art:

Okay, Dr. Lai, what treatment strategies are available for genetically adverse risk patients, as well as measurable residual disease or MRD-positive AML patients?

Dr. Catherine Lai:

Yeah, so I’ll take those two separately. So for the genetically adverse patients, and so just also as an update in 2020, in the summer of 2022, both the World Health Organization and the European Leukemia Network, they both updated their guidelines. So it’s called WHO 2022 and ELN 2022 in terms of how we help prognostic and risk-stratify our patients.

And so for the ELN 2022, there are a handful of additional mutations that do put patients at adverse risk, and so it would be good just to know to bring up with your physician, which in risk category am I in? 

And so in general, for the adverse risk patients, the long-term goal is bone marrow transplant once in complete remission. And so I would say that the initial treatment hasn’t really changed, but we are recommending more patients for transplant because there are a larger number of patients who are now in that adverse risk category.

For the MRD-positive patients, there are clinical trials that are targeted, are enrolling specifically for MRD-positive patients for the most part, once you’re in complete remission, if you’re MRD-positive, you just would continue on your current therapy. And for some patients who continue their current therapy that MRD, that MRD will eventually go away.

If they are done with therapy, it would be something that you would want to monitor very closely, and at the site at the time at which that that MRD is growing, you would want to consider re-initiating treatment, although that is not standard, so it’s a very tailored and individual discussion with your physician.

So, I say, in general, the activation tips for genetically adverse risk, it would be to have a conversation about whether or not you should be going to transplant. And for MRD-positive patients, I would say is to ask about how frequently my testing should be done to monitor for MRD, MRD-positive disease. 

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What Is MRD-Positive Acute Myeloid Leukemia?

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What Is MRD-Positive Acute Myeloid Leukemia? from Patient Empowerment Network on Vimeo.

What do acute myeloid leukemia (AML) patients need to know about MRD-positive AML? Dr. Catherine Lai from Penn Medicine discusses minimal residual disease (MRD). Learn about the meaning of MRD, complete remission, and MRD testing methods.

[ACT]IVATION TIP from Dr. Lai: “Ask if MRD testing can be done on your bone marrow biopsy at the time at which you or after you’ve had your chemotherapy.” 

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Transcript: 

Art:

Dr. Lai, what is MRD-positive AML?

Dr. Catherine Lai:

So, that’s a really good question. And to answer that question, I’m going to actually answer a different question, which is, What is the definition of complete remission? So the definition of complete remission is when we do a bone marrow biopsy, and we have less than 5 percent of those blasts or leukemia cells in the bone marrow, and that is also in the setting of a relatively normal immune system or normal other blood counts have improved, so that your neutrophil count is above 1,000, and your platelet count is above 100,000. So, MRD, which stands for measurable residual disease, means that you’re in complete remission, so you have less than 5 percent blasts, but you’re more than zero.

And we, in general, when patients who are MRD-positive, we know that if you were to do nothing, that those patients have a high likelihood of relapse. We know for the patients who are going to transplant, if you’re MRD-positive before transplant, those patients also have a higher likelihood of relapsing after transplant. And so we tend to monitor it if possible…the tricky thing is, is that there is not a standard way to measure MRD testing as of yet, the common approaches are right now are with either flow cytometry or with PCR or next-generation sequencing, if you have a particular targeted mutation that we can follow.

So your activation from that standpoint is to ask if MRD testing can be done on your bone marrow biopsy at the time at which you or after you’ve had your chemotherapy. 

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What Is FLT3-Mutated Acute Myeloid Leukemia?

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What Is FLT3-Mutated Acute Myeloid Leukemia? from Patient Empowerment Network on Vimeo.

Some acute myeloid leukemia (AML) patients may have an FLT3 mutation. Dr. Catherine Lai from Penn Medicine shares insight about the two types of FLT3 mutation, treatment options for FLT3-mutated AML, and progress in research

[ACT]IVATION TIP from Dr. Lai: “Ask your oncologist, if your FLT3 mutation testing was done, ask which type of mutation they have, if it’s the ITD or TKD, if they are FLT3-positive and what the drug options are available for them.”

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BIPOC Patients Living with AML | Mortality Rate and Favorable Genetics

Transcript: 

Art: 

Dr. Lai, what is FLT3 mutated AML and what treatment options do patients with FLT3 AML have?

Dr. Catherine Lai: 

Yeah, so FLT3, FLT3 mutations occur in about 25 percent to 30 percent of patients. There are two different types of FLT3 mutations. There’s a FLT3, the ITD mutation and the FLT3, the TKD mutation. They just are there, different parts of the mutation on different parts of the cell, and so how I think about that is, if you think of a leukemia cell and each leukemias has a different color-coded flag, and so the FLT3 mutation I think of is just having a specific color coding, and while a FLT3 mutation in general does predict for a worse prognosis for patients, we do have targeted treatments. In a newly diagnosed setting, we have midostaurin (Rydapt), which is added to intensive chemotherapy for those fit enough to tolerate it. 

And in the relapsed refractory setting, we have a medication called gilteritinib (Xospata), which is given as a single agent, so a chemo pill, and that was compared to all types of chemotherapy, both intensive and low intensive chemotherapy, and that pill alone and the refractory and relapsed setting was better than either of the chemotherapies alone, so we’ve made a lot of progress for the FLT3-mutated patients to the majority of those patients end up going to transplant if possible, and so there are studies that are looking at FLT3 inhibitors in the post-transplant setting to also help improve long-term survival and overall survival. So the activation tip from that standpoint, that is to ask your oncologist, if your FLT3 mutation testing was done, ask which type of mutation they have, if it’s the ITD or TKD, if they are FLT3-positive and what the drug options are available for them. 

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What Are the Latest Acute Myeloid Leukemia Therapies?

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What Are the Latest Acute Myeloid Leukemia Therapies? from Patient Empowerment Network on Vimeo.

What are the latest treatments in acute myeloid leukemia (AML)? Dr. Catherine Lai from Penn Medicine discusses the increase in available AML treatments. Learn about combination therapies and treatment options for patients with IDH1, IDH2, and FLT3 mutations.

[ACT]IVATION TIP from Dr. Lai: “Ask your physician and your oncologist when you’re talking with them about what all the newest therapies are and what would be specifically the best treatment for their specific leukemia with respect to the different mutations.”

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What Promising AML Treatments Are Available for Newly Diagnosed Patients?

Transcript: 

Art:

Dr. Lai, for newly diagnosed AML patients, what are the latest available therapies?

Dr. Catherine Lai:

That’s a great question. The last, I would say, a handful of years have really seen a dramatic increase in the number of new treatment options for AML patients, specifically since 2017, the FDA has approved 10 new drugs for AML, that’s both for patients who are newly diagnosed and in the relapsed refractory setting.

And so what I would say is that we break our patients into two different categories in terms of being able to tolerate intensive chemotherapy versus non-intensive chemotherapy, and as well as looking at specifically targeted mutations that patients may have so that we can better understand the disease but also treat these patients more specifically to try to maximize efficacy while minimizing toxicity. 

And so specifically, I would say for patients who have FLT3 mutations, there are drugs such as midostaurin (Rydapt) and gilteritinib (Xospata), there are drugs for mutations in IDH1 and IDH2, enasidenib (Idhifa) and ivosidenib (Tibsovo) and recently, or in December of  2022, olutasidenib (Rezlidhia) was also approved for IDH1-mutated patients as well.

We have a general targeted agent that’s an oral chemotherapy that probably has made the biggest difference in how we treat patients called venetoclax (Venclexta), and that’s used in combination with azacitidine (Onureg) or decitabine (Dacogen), or low dose cytarabine (Cytosar).

Although most commonly in the United States, we use azacitidine or decitabine in combination with the venetoclax, and that I think is really what I’d say has been practice changing for the most part, in terms of both increasing the complete remission rates as well as the overall survival for these patients. So I would say there are a lot of new drugs. It is all very exciting.

The biggest activation tip in terms of takeaways is to ask your physician and your oncologist when you’re talking with them about what all the newest therapies are and what would be specifically the best treatment for their specific leukemia with respect to the different mutations.

Art:

Okay. Dr. Lai, what are the latest approaches to combination chemotherapy to treat AML?

Dr. Catherine Lai:

So, the latest approaches for combination chemotherapy would be in the combination of a hypomethylating agent, azacitidine or decitabine in combination with venetoclax. This is the most practice-changing combination that has been approved since 2017 to 2018, and now more recently, what’s been happening is now looking, so we call that a doublet, and now it’s been looking at…what we’ve been studying is now whether or not triplets are more effective, when we do have triple combinations, we do see an increase in toxicity and so on, we haven’t come up with the right algorithm in terms of what that exact formula should be, but often I think about it in kind of a three-fold in terms of wins the right time, what’s the right combination, and how do we see in the drugs, and I think the sequencing is the biggest thing that we don’t yet know, and how do we combine the two different..two different drugs in a way, and how do we give them in a way that will maximize efficacy, will minimize the toxicity, so as an example is, Do we give two drugs for a specific period of time, and then after some determined time point, do we…

And change it to a different set of combination of drugs to make sure that patients are getting the most benefit of the drugs, and we don’t know that yet, but I think that that’s where the general direction…where the landscape is heading, so the activation tip I would take home from this is just to have a conversation with your physician about potential clinical trials and how combination therapies are being used. 

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Quizartinib in FLT3-ITD-Positive AML

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Introduction 

I generally think of treatments for AML as old, meaning they were around when I was diagnosed in 1992, or new ones that were developed after that. In the first 25 or so years since I was diagnosed, there were very few new treatments. In the last 5-7 years, however, there have been several new treatments. There are targeted treatments like, Ivosidenib (which I wrote about in November: Ivosidenib and Azacitidine for IDH1-Mutated AML) as well as Ventoclax which is used with a number of different drugs (Azacitidine, Decitibine and low dose Ara C). This post is about a new (to the U.S. anyway) drug, Quizartinib, which is used in AML patients who have a specific mutation FLT3 (fms-like tyrosine kinase 3), specifically a FLT3-ITD (internal tandem duplication) mutation. 

Overview of FLT-3 

There are two different mutations in the FLT3 gene, ITD and tyrosine kinase domain mutations (TKD). The most common mutation in AML is in the FLT3 gene. About 30% of AML patients have an FlT3 mutation, with FLT3-ITD mutations more common than FLT3-TKD ones. Some of the existing drugs for FLT3 mutations treat both. Midostaurin (Rydapt) and Gilteritinib (Xospata) are used in patients with either FLT3 mutation. Quizartinib is only used to treat patients with a FLT3-ITD mutation. 

Current Study of Quizartinib 

The current study, the results of which were presented at the 2022 European Hematology Association (EHA) Annual Meeting in Vienna, tested standard chemotherapy with Quizartinib or with a placebo, followed by maintenance with Quizartinib or placebo for 3 years. More than 500 patients with a FLT3-ITD mutation were treated in the trial. Quizartinib or a placebo were added to the “7+3” standard induction therapy, which consists of 7 days of cytarabine (Ara-C) plus 3 days of daunorubicin or idarubicin. Patients who were in remission after induction either went on to up to 4 rounds of high dose cytarabine consolidation with Quizartinib or placebo and/or an allogeneic (donor) stem cell transplant, followed by up to 3 years of maintenance therapy with Quizartinib or placebo. 

The patients who received Quizartinib had a median overall survival of more than double the patients who received the placebo. Almost all patients in both arms experienced side effects of the treatment (emergent adverse events or AEs). This is not a surprise, most patients treated for AML have significant side effects. Patients who received Quizartinib had more side effects, in particular there was a higher incidence of significant neutropenia (low white counts) and more patients who received Quizartinib discontinued treatment because of adverse events. There were 56 treatment related deaths in the trial, somewhat more in those who received Quizartinib. 

Quizartinib looks like a promising treatment for FLT3-ITD AML patients. I believe that this is the only randomized (Phase III) trial that has been completed of a drug that treats mutations in the FLT-3 gene along with standard chemotherapy. It will be interesting to see how it compares to other drugs for patients with FLT-3 mutations. On the downside, it is only used for FLT3-ITD mutations, unlike Midostaurin and Gilteritinib. 

Further Reading 

Quizartinib Doubles Overall Survival in FLT3-ITD-Positive AML, article from Medscape on the trial of Quizartinib and Chemotherapy, June 13, 2022. 

Quizartinib Prolonged Survival VS Placebo Plus Intensive Induction and Consolidation Therapy Followed by Single-Agent Continuation in Patients Aged 18-75 Years With Newly Diagnosed FLT3-ITD+ AML, from 2022 European Hematology Association (EHA) Annual Meeting in Vienna. 

Daiichi Sankyo’s survival data mean it may finally be ready to compete with Novartis’, Astellas’ marketed AML meds, an article from Fierce Biotech, which covers the biotechnology industry. 

Xospata FDA Approval History, from Drugs.com, gives a history of the FDA approval of Xospata (gilteritinib). 

Overcoming Resistance: FLT3 Inhibitors Past, Present, Future and the Challenge of Cure, Capelli, D.; Menotti, D.; Fiorentini, A.; Saraceni, F.; Olivieri, A. Cancers 2022, 14, 4315. A long journal article on treating FLT-3 AML (I have not read all of it). 

FLT3 Inhibitor Quizartinib Improves Survival in AML reports on an older study showing patients with relapsed/refractory FLT3-ITD-positive AML have improved survival with Quizartinib, given as a single agent compared with standard-of-care chemotherapy. Medscape, July 02, 2018. 

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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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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.

See More From INSIST! AML

Related Resources:

How Does the Presence of Molecular Markers Affect AML Care

 Diagnosing and Treating AML_ What Testing Is Essential

 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.

See More From INSIST! AML

Related Resources:

Diagnosing and Treating AML_ What Testing Is Essential

 Advances in AML Research _ Where Do Clinical Trials Fit In

 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.