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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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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AML Clinical Trials Critical to Treatment Breakthroughs and Improvements

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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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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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.

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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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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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 Does Maintenance Therapy Have a Role in AML Care

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.  

The Benefits of Being Pro-Active in Your AML Care

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The Benefits of Being Pro-Active in Your AML Care from Patient Empowerment Network on Vimeo.

Dr. Eytan Stein, an AML expert, discusses the importance of communicating regularly with your healthcare team and shares what makes him hopeful about the future of AML care.

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 it essential for patients to share any issues they may be having with their healthcare team, specifically, sharing their symptoms and side effects?   

Dr. Eytan Stein:

Well, it’s important because we want to help you. I mean, I think that’s what it comes down to. All of us, whether it’s your doctor or your nurses or your nurse practitioner or physician’s assistant or anyone who is part of the healthcare system, we went into this business to help people. I mean, we knew what we were getting into when we went into this, and we want to help people. And one of the ways you help people is you help with their symptoms. So, if you’re not feeling well, you call up, and you say, “I’m not feeling well,” we can help you with that. You shouldn’t suffer in silence.  

I sometimes have patients who will say to me, “Oh, I was going to call you, but I didn’t want to bother you.” You’re not bothering us. This is what – it’s not like you’re calling and asking for mortgage advice, right? This is what we do. So, it’s very important to call us because the other thing is that you’re going to be more – it’s more likely that you’ll be able to complete your treatment if we manage the side effects that you’re having rather than just ignoring them.  

Katherine Banwell:

What advice do you have for patients to help them feel confident in speaking up and becoming a partner in their own care? 

Dr. Eytan Stein:

My advice is, speak up. You just speak up. It’s very important. It’s your – you know, at the end of the day, this is a disease that you are experiencing. Your doctor is there to partner with you and to guide you, but it’s your body. It’s your disease, and you need to be very vocal in what you’re experiencing and advocate for yourself.  

Katherine Banwell:

If a patient has difficulty voicing their questions or concerns, are there members of the support staff who could help?  

Dr. Eytan Stein:

Most centers have a social worker on staff that can help them out. I highly, highly encourage all of my patients to meet with a therapist or a psychologist that specializes in taking care of patients with cancer. I have become more vocal about this that I see really, it’s probably the best thing a patient can do for themselves, and there’s no downside. If you don’t like it, you don’t have to go back. You can do one appointment and not go back. But that can be extremely helpful, extremely helpful.  

So, it’s important in both ways. You need to alert your doctor that you might be feeling one way, but I think it’s also on the doctor to sort of take visual cues from the patient when they see them to understand what they might need and to make those kind of recommendations.  

Katherine Banwell:

Yeah. As we close out our conversation, Dr. Stein, I wanted to get your take on the future of AML. What makes you hopeful?  

Dr. Eytan Stein:

Oh, so many things make me hopeful. I mean, we understand this disease so much more than we understood it even 10 years ago. There are all sorts of new treatments that are being developed. We’re improving the survival of our patients with the new treatments that have already been approved over the past 10 years. And I really think the golden age of AML treatment is upon us, and I really think that – and some people might think I’m crazy – but I really think that by the time I’m done with this, you know, one day, I’ll get too old, and I’ll decide I need to go retire and spend time with my family. But I think by that time, we’re going to be curing the vast majority of our patients. 

Katherine Banwell:

That’s so positive. It’s great to hear that there’s been so much advancement and that there’s so much hope out there for AML patients.  

I want to thank you so much for taking the time to join us today, Dr. Stein.  

Dr. Eytan Stein:

Okay, thank you. It was really nice to be here.   

Managing Your Oral AML Treatment | Tips for Staying on Schedule

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Managing Your Oral AML Treatment | Tips for Staying on Schedule from Patient Empowerment Network on Vimeo.

With oral AML therapies becoming more available, patients now play a role in administering their own treatment. Dr. Eytan Stein shares tips for patients managing their at-home treatment regimens.

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:

With more oral therapies becoming available, patients now have a role in self-administering their treatment. So, what happens if a patient forgets to take a medication? Does that impact its effectiveness? 

Dr. Eytan Stein:

The easy answer to that question is probably not. You know, if you forget to take a medication for three weeks, that’s not a good thing, but if there’s a – you know, this happens all the time, right?  

You’re busy, and you just forget. If you forget to take a medication one night or one day, it almost certainly is not going to make a huge difference. Having said that, you shouldn’t see that as license to not be careful. So, it is important to try. So, set an alarm; put out a pill container do the kinds of things that can help you.  

The other thing, there is a certain what I would call pill fatigue that sets in. Often, patients with AML are taking multiple medications at multiple times a day, and it can be hard. And at my center, we have pharmacists who do a lot of different things, but one of the things they can help with is sort of streamlining patients’ pill burden to make it easier for them to remember and to take the medications when they’re supposed to take them. 

Katherine Banwell:

When a patient does forget to take a dose or even a couple of days’ doses, should they call their healthcare team and let them know? 

Dr. Eytan Stein:

Yes, always call. Always call.  

Disease Monitoring: Is My AML Treatment Working?

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Disease Monitoring: Is My AML Treatment Working? from Patient Empowerment Network on Vimeo.

Dr. Eytan Stein explains how AML treatment effectiveness is monitored and why it’s essential for patients to report any symptoms or side effects to their healthcare team.

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:

Once treatment has begun, Dr. Stein, how do you know if it’s working?  

Dr. Eytan Stein:

So, that’s a good question. So, the good thing about acute myeloid leukemia when it comes to understanding what’s going on, you know, it’s a disease of the bone marrow cells. And we do bone marrow biopsies to see how things are doing. But no one likes a bone marrow biopsy. It can be a somewhat uncomfortable procedure.  

Katherine Banwell:

How often would a patient need to have a biopsy? 

Dr. Eytan Stein:

Yeah, so they have bone marrow biopsies at diagnosis, and then they often will have bone marrow biopsies two weeks to a month later.  

And then, if they’re in remission, basically any time you think if you want to check to see if they’re in remission or if you suspect the patient is relapsing. Then, you would do a bone marrow biopsy. But what I was getting at is that but you have blood. And the blood is kind of like the bellwether of what’s going on in the bone marrow.  

So, the analogy I use for my patients is, you know, when you’re driving your car and you have – you know, you don’t open the hood every day to make sure the car is running okay. You know, you’re driving your car, and if your car starts making a funny clinking sound, that’s when you open the hood.  

So, the blood is like the clinking sound. If you see something going wrong in the blood, that’s when you know you’ve got to open the hood and look under the hood. If the car is running just fine and you don’t see anything wrong in the blood, using the analogy, maybe you don’t need to do a bone marrow biopsy. 

Katherine Banwell:

What if a treatment isn’t working? What if it stops working or if the patient relapses? What do you do then? 

Dr. Eytan Stein:

Yeah, so when a patient relapses, which unfortunately happens more than we want it to, it’s important number one to do another bone marrow biopsy and at that point, do that mutational testing again because the mutations that are present at the time of diagnosis are not necessarily going to be present at the time of relapse, and sometimes, a new mutation might occur at the time of relapse.  

And again, what that mutational profile shows can help determine what the next best treatment for the patient is. There might be standard-of-care therapies. More chemotherapy might be recommended.  

When a patient relapses, I usually – excuse me – try to get them on a clinical trial because that’s the point where I think clinical trial drugs really have potentially major benefit for the patients, to help get them back into remission. 

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.  

Considerations When Choosing an AML Treatment

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Considerations When Choosing an AML Treatment from Patient Empowerment Network on Vimeo.

AML expert Dr. Eytan Stein reviews factors that should be considered when choosing an AML treatment approach, including potential side effects, age, and patient preference. 

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:

All patients are different, of course, and what might work for one person might not be appropriate for another. How do you choose which treatment is right for a patient? 

Dr. Eytan Stein:

So, it’s an individualized decision. So, what you’re talking to the patient, as we talked about at the very beginning, is you really need to understand the patient’s goals for treatment. You need to understand the anticipated benefit of the treatment that you’re offering and need to understand the side effects of the treatment. 

So, and that sort of becomes the puzzle that you work with the patient at putting together. That is how well do I expect this treatment to work? What are the potential side effects of the treatment, and what are the patient’s goals? And when you sort of lay all those different pieces out, you then usually come up with something that becomes pretty clear what the best thing to do is.  

So, I’ll give you just a very concrete example of this. Sometimes, we have treatments where the medical data would suggest that they might work as well as one another, right? There’s no clear difference between each of the two treatments. But maybe one of the two treatments requires you to be in the hospital, and one of the treatments allows you to be at home.  

So, that’s an important discussion to have with the patient because some patients, believe it or not, want to be in the hospital, because they’re worried about being at home and having to manage this all themselves. Some patients don’t want to be in the hospital. Some patients want to be at home, because they’re scared of the hospital, or they’re worried the food’s going to be terrible.  

And then, that would be important in helping the patient make the decision for their treatment. 

Katherine Banwell:

Right. You mentioned earlier, Dr. Stein, the difference in ages and how you would treat different people depending on their age. So, when you’re choosing a treatment, you obviously look at age. What else? Things like comorbidities? 

Dr. Eytan Stein:

Yeah, so age, so I’m not ageist. So, it’s more that as people get older – and this is just a fact of life – as everyone gets older, their organs don’t work quite as well anymore, right? Things start breaking down as you get older. So, certain treatments aren’t appropriate for older people because the treatments a younger person, because their organs are working at 100 percent, may be able to handle it, while an older person, where their organs might only be working at 60, 70 percent, the treatment might not be as good of a choice for them. 

So, that’s what I mean. So, as people age, their comorbidities increase. So, we always look at comorbidities, and if you had an 80-year-old that was running marathons, I might think about their treatment differently than an 80-year-old who is not running marathons. But most 80- and 85-year-olds aren’t running marathons, so that’s why we sometimes think about their treatment differently. 

What Are Current and Emerging AML Treatment Approaches?

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What Are Current and Emerging AML Treatment Approaches? from Patient Empowerment Network on Vimeo.

AML Expert Dr. Eytan Stein provides an overview of current and emerging treatment approaches for people living with AML.

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.

See More from Thrive AML

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Disease Monitoring: Is My AML Treatment Working?

Transcript:

Katherine Banwell:

What are the treatment types available to AML patients? You mentioned chemotherapy. What else is there? 

Dr. Eytan Stein:

Yeah, so if I was having this discussion with you, even when I first started my career back in 2013, all I would’ve been talking to you about was induction chemotherapy and maybe a lower-dose chemotherapy called hypomethylating agents.  

I think one thing that really needs to be recognized is that the advances we’ve made for the treatment of acute myeloid leukemia, over the past 10 years, have been just remarkable. We’ve had a number up to nine drug approvals over the past 10 years, and those therapies fall into the following categories.  

We now have therapies outside the strong induction consolidation we talked about. We have therapies such as targeted therapies that target specific gene mutations that are present in patients with acute myeloid leukemia. Those are often oral therapies that patients can take at home. And we have very effective therapies for older patients who usually can’t handle the side effects of induction chemotherapy. That’s the combination of a type of drug called a hypomethylating agent with a very, very powerful targeted drug called a BCL-2 inhibitor.  

One of those drugs, that drug is called venetoclax. That’s the one that’s FDA-approved. And the combination of those hypomethylating agents and venetoclax, has really changed the paradigm for how we treat older patients with acute myeloid leukemia, led to many patients who have been able to live much longer than they would have before this therapy came about.  

You know, there are other therapies that are in development, but I don’t know if we’ll end up talking about that a little bit later. But there are therapies such as immunotherapy, which has gotten a lot of press for other kinds of cancers, like one cancer called the rectal cancer, that aren’t yet approved for acute myeloid leukemia but are being developed for acute myeloid leukemia.   

So, the future of acute – the current treatments for acute myeloid leukemia are dramatically better than they were 10 years ago, and I would anticipate that we’re going to continue to see these kind of advances over the next 10 years.  

Katherine Banwell:

What about stem cell transplant? Who might be right for that? Who might be eligible? 

Dr. Eytan Stein:

Yeah, so let’s go back to the discussion a little bit about consolidation chemotherapy. So, when you have a patient that gets induction chemotherapy or gets any therapy – it doesn’t have to be chemotherapy – to put their disease into remission, for a large group of patients, we think that the best way to cure their disease is to do something called a stem cell transplant.  

So, what’s a stem cell transplant? What it is not is like a heart transplant or a liver transplant, which patients often don’t realize.  

So, it’s not a procedure where an organ is being transplanted through a surgical procedure. What it is is it’s acknowledging that the cause of acute myeloid leukemia is that the most primitive cells in the bone marrow, called the stem cells, are the cause of the disease. And the chemotherapies that we give patients to get them into remission don’t always eradicate those bad stem cells.  

So, what we’re able to do once a patient is in remission is we try to get them new stem cells. How do you get a patient new stem cells? Well, you go to a donor, and there’s a donor bank of people who have volunteered to donate stem cells to patients with acute myeloid leukemia. You go to the donor bank, and then you give chemotherapy to the patient to sort of wipe out their bad stem cells, and then you give them new stem cells that will hopefully permanently eradicate the disease. 

What ends up happening is that a large group of patients with acute myeloid leukemia end up being referred for a stem cell transplant. The reason is twofold. You know, it used to be – I keep talking about the past. I’m getting older, and so now I can talk about the past.  

Yeah. So, it used to be that stem cell transplants were really reserved to people less than 65 years old.  

But our advances in our ability to do stem cell transplants has allowed for us to now successfully do stem cell transplants on patients, even into their upper 70s and sometimes even at the age of 80.  

Katherine Banwell:

Where do clinical trials fit in to all of this? 

Dr. Eytan Stein:

Ah. So, clinical trials are extraordinarily important for a variety of reasons. Clinical trials are important because the only way we make advances on a societal level in the treatment of acute myeloid leukemia is by patients who are willing to participate in clinical trials. All of the – because these are trials that are testing new therapies with the goal of improving the survival and the quality of life of patients with acute myeloid leukemia. All these drugs I just talked about that have been approved over the past 10 years, they never would’ve been approved if patients hadn’t agreed to participate in clinical trials. So, that’s something that’s number one that’s very important.  

But on a – forget the societal level for a second. On a patient-specific level, a clinical trial can potentially benefit a patient because it offers a patient access to a new, exciting therapy that may really help in improving their outcome of having acute myeloid leukemia.  

Katherine Banwell:

Yeah. You mentioned emerging therapies. What are some of those? 

Dr. Eytan Stein:

Oh, there’s so many. So, it’s hard to talk about all of them, but I think there are targeted therapies – I think if you sort of break them up into sort of broad buckets, there are new targeted therapies that are being developed for subsets of patients with acute myeloid leukemia. One of the ones I’ve been working on pretty heavily over the past few years is a kind of drug called a menin inhibitor. This is an oral medication that is given to patients of acute myeloid leukemia who have certain genetic abnormalities, specifically either a mutation in a gene called NPM1, or a what is called a rearrangement in a gene called MLL.  

So, that’s a group of – that menin inhibition seems to be extraordinarily effective in treating patients, at least from the early data, for those specific subtypes of acute leukemia.  

The other therapies that are really getting a lot of play now are the immunotherapies, which I mentioned a second ago. There are immunotherapies that work to – called bispecific immunotherapies where what happens is it works to harness the immune system to kill the cancer cells. You may have heard a lot about CAR T-cell therapy, which is another way of harnessing the immune system and engineering immune cells to target acute myeloid leukemia cells. And the other thing I want to point out is that even if you don’t have a new therapy against a new target, you can imagine now that we’ve got all these 10 new approved drugs.  

But what we’re trying to figure out – one of the things we’re trying to figure out over the past few years has been what’s the best way to give these new drugs? What kind of combinations can you put them in that might make things even better? Maybe you should give two of those drugs first and then give another drug afterwards. And a lot of the research that’s being done now is being done to understand the best sequencing and combinations of drugs with the drugs that we already have approved.