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Elevate | What You Should Know About Your Role in AML Treatment and Care Decisions Resource Guide

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Elevate | What You Should Know About Your Role in AML Treatment and Care Decisions

Elevate | What You Should Know About Your Role in AML Treatment and Care Decisions from Patient Empowerment Network on Vimeo.

How can you elevate your AML care and treatment? AML expert Dr. Gail Roboz discusses the importance of participating in AML treatment decisions, reviews key factors that may impact therapy options, and shares advice for advocating for yourself.
 
Dr. Gail Roboz is director of the Clinical and Translational Leukemia Programs and professor of medicine at Weill Cornell Medicine and the New York Presbyterian Hospital. Learn more about Dr. Roboz.
 

Related Resources:

FLT3 inhibitors for AML Update

Thriving With AML | Advice for Setting Goals and Making Treatment Decisions

Thriving With AML | Advice for Setting Goals and Making Treatment Decisions

Expert Advice | Managing AML Symptoms and Treatment Side Effects

Expert Advice | Managing AML Symptoms and Treatment Side Effects

Transcript: 

Katherine Banwell:

Hello, and welcome. I’m your host, Katherine Banwell. It’s no secret that the quality-of-care patients receive can vary, and patients who are educated about their condition and involved in their care may have improved outcomes. That’s why the Patient Empowerment Network created the Elevate series, to help AML patients and their care partners feel well-informed when making treatment decisions with their healthcare team. 

In today’s program, an AML expert will join us to share advice for accessing better overall care. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining us is Dr. Gail Roboz. Dr. Roboz, would you please introduce yourself? 

Dr. Gail Roboz:

Absolutely. Thank you so much for having me. My name is Gail Roboz. I’m a professor of medicine and director of the clinical and translational leukemia programs at Weill Cornell Medicine and the NewYork-Presbyterian Hospital in New York City. Thank you again for having me. 

Katherine Banwell:

Well, thank you so much for joining us today. We really appreciate it. I’d like to start by discussing your role as a researcher. You’re on the frontlines for advancements in the AML field. What led you here, and why is it important to you? 

Dr. Gail Roboz:

So, I’m actually asked that question quite frequently, because AML is a challenging, difficult, scary disease, and people don’t necessarily assume that somebody in medical school would gravitate toward it. 

But I have to say that what is incredibly fascinating back then and now about leukemia is the continuous access to the disease. Patients will maybe giggle or groan as I’m saying that, because you can get a blood sample really anytime. You can even get a bone marrow sample anytime, although patients don’t enjoy that so much. 

But from a research perspective, it is absolutely extraordinary to be dealing with a disease where you can, in real time, truly run back and forth to a laboratory and see what’s happening, what is the new drug or the old drug doing, what’s happening with the patient, and I would say that from a fascination of a medical student perspective that grabbed me then and still does today.  

Katherine Banwell:

When it comes to choosing therapy for AML, it’s important to work with your healthcare team to identify what will work best for you, the patient. So, I’d like to know how you define shared decision-making.  

Dr. Gail Roboz:

The problem with AML sometimes is that it can be such an acute, emergency-type of presentation and urgent decision-making that I think your question is almost right out of the gate for some patients that will, “Wait, I don’t even have a minute, here. How do I build a team, do the research, look online if people are telling me that I’m in the middle of an emergency?”  

That isn’t always the case for acute leukemia, but it sometimes is. I think that what happens in AML in particular for patients is a building of knowledge and a building of the team, and figuring out, first of all, where am I when I am being told this diagnosis, and is it really an emergency? Do I have to make decisions really right now, because is it life-threatening today, I don’t have time to look around? Or do I have a minute to pause and get more information? 

I definitely feel that with the Internet era and with so much connection between doctors and teams, there is much more ability to reach out instantaneously for doctors, too, to get advice on a patient who might be in a smaller hospital that doesn’t have AML experience. But I think that the first thing is to try to figure out very, very quickly, what needs to happen to me as a patient immediately, and what can wait a minute, so that I can figure out what am I being told, and what are my options?  

Katherine Banwell:

Right, right. It can be confusing for patients, just finding out this new information. Part of making care decisions is setting goals. What are AML treatment goals, and how are they determined?   

Dr. Gail Roboz:

I would say that leaving cure on the table from the beginning is always a good place to start, because you want to figure out, first of all, what am I dealing with? What are the actual options?   

But when AML strikes, and a patient who has multiple medical conditions or comorbidities that are truly compromising function independently of the diagnosis of AML, that’s going to be a special path of what is actually reasonable for someone who is terribly medically ill or otherwise frail right from the beginning? That can be defining goals, but I think from the beginning, the best thing is to leave everything on the table. What can actually be done to make me better, first of all, to get me out of my immediate trouble? What can be done to make me better, and if I’m getting better, well, I like that, how do I stay there?  

What can be done to hang on to the state of ‘better,’ which is sometimes defined as remission? In AML, the goal is to get the bone marrow working again, functioning again, get rid of the acute emergency problem, if there is one, which there may or may not be in acute leukemia. 

Sometimes it’s truly an emergency, and sometimes it isn’t. But once I get better, can I stay there? What is required to keep me with a working bone marrow for as long as possible? 

But once you are starting to sort through the diagnosis, you realize that saying that somebody has acute myeloid leukemia is not telling me nearly enough information. This is a disease that is what we call biologically heterogeneous, which means there are lots of different forms. It’s like saying you’re sick. What exactly does that mean? There are lots of things that can make you sick. There are lots of different subtypes of AML, and fairly quickly in most institutions, we start getting back some information specifically on the subtype and biological characteristics of the disease.  

This can be very, very important in the initial treatment planning, and depending on where you are, the information that you get back can sometimes take 24 hours, 48 hours, 72 hours, a week. So, you start learning very quickly though that, “If I’m not in a complete emergency that requires instantaneous treatment, can I get back more information about the biological subtype of the disease so that I can start treatment planning of what is my best option right out of the gate?” That’s usually called induction, or the first therapy that you’re going to get with the goal, ‘getting rid of leukemia cells and getting into remission.’ That’s part one, and then everything that comes after that is about keeping you in remission.  

But for the initial goal, what is the therapy that the patient needs to get to get into remission? In order to figure that out, the good news is there are a lot of different ways to slice and dice getting into remission, and actually, it used to be such a weighty decision. 

Now, I would actually encourage people to – not relax, you can never use the word ‘relax’ with acute leukemia. But there are several different induction strategies for most patients that would be okay.  

So, even if you get started with one strategy and you hear five days later that another doctor might do something different, there are a lot of ways to safely get into remission. I think everybody should be pleased about the fact that we’re doing much better than we used to for patients across the board, all the way from children to much older adults, to safely getting people into remission. 

Katherine Banwell:

Right. So, what sort of factors then do you take into consideration when you’re choosing a therapy? 

Dr. Gail Roboz:

So, out of the gate, there are the patients that I think I referred to earlier who truly, truly are in situations based on their other diseases that there are certain treatments we would just cross out right out of the gate.  

If there are patients with very, very severely compromised cardiac or renal or lung function or are terribly ill from other conditions, AML doctors will right out of the gate for those patients eliminate certain treatments. But absent that scenario, what we try to look for is the biology of the disease. Not look at the age, not look at the comorbidities unless they are so severe that they make obvious certain choices. 

But rather, what I like to do is say, “What kind of AML is this, and what is the best treatment that I have to get this patient into remission?” And then ask the question, “can this particular patient handle this therapy?” Sometimes, these days, there actually may be more than one route to get to remission depending on the biology of the disease, and then, if that’s the case, then I can start getting picky and look at the individual patient. Where does the patient live? Who’s the patient’s family? What other diseases has the patient been treated for?  

Is there something that I can use? If I have a choice, if there are a couple of different things that might work, how do I fit the treatment to best take care of the needs of this particular patient? If I don’t have choices, then my question is, “Okay, how do I get this patient through my one therapy that I think is the truly, truly best option?” 

Katherine Banwell:

Okay. I’d like to turn to test results for a moment. What sort of tests should be done following an AML diagnosis?  

Dr. Gail Roboz:

We often generally recommend a bone marrow biopsy, even if we know we can make the diagnosis from a blood test, because even though the bone marrow biopsy is not the most fun test in the world, it does offer better information for follow-up care than what you can get initially from the blood. 

So, every once in a while, we do have a patient for whom a bone marrow biopsy itself for whatever reason can’t be done. But almost always, we need a bone marrow biopsy, and on that biopsy, you’re going to look under the microscope and see what the cells look like. You’re going to get back standard testing, which is called flow cytometry, which is going to tell the difference between what are the different cells that you’re seeing under the microscope. 

But then you’re actually going to get progressively much more fancy testing, including things called chromosomes or cytogenetics, and then ultimately, the majority of patients, if at all possible, will be having mutational testing to identify certain subgroups of AML that benefit from very particular treatments. Next-generation sequencing, PCR, fusion proteins, FISH, cytogenetics, I can go on and on with all kinds of terminology that is very confusing, even to hematology fellows, let alone to patients.  

Usually, we use a combination of tests to decide, “Is this patient likely to be able to be cured with chemotherapy alone, or might this patient benefit from a stem cell transplant from somebody else after they go into remission?” 

That’s basically what the prognostic scoring systems used to be asking, but now it’s a lot more complicated than that. Because even in the favorable categories, even in the adverse categories, where there used to be very little subtlety, now there is a lot of subtlety. 

It’s all about defining getting into remission, and what do I give you once you’re in remission to keep you there? It’s no longer this windshield wiper thing of good, bad, transplant, no transplant. There’s a lot more to AML than there used to be. 

Katherine Banwell:

I’d like to add that if you, the viewer, are interested in learning more about AML testing and treatment, PEN has a number of resources available for you. You can find these at powerfulpatients.org/AML, or by scanning the QR code on your screen.  

Before we get into specific treatment types, Dr. Roboz, would you provide a brief explanation of the phases of therapy for AML? You mentioned induction therapy earlier. Would you tell us what that is? 

Dr. Gail Roboz:

Yeah. So, here, too, I have to say that it’s more confusing than it used to be for the following reasons. So, historically and currently, we typically talk about induction as the first therapy that you’re going to get to get into remission.  

Then, the treatment paradigm is you do something to get into remission; do some treatment to get into remission. After that, in the realm of post-remission therapy, there are different things that can happen. There can be something called consolidation, which might be another round of chemotherapy. Some patients get consolidation, some patients don’t. After consolidation, there can be a transplant.  

So, you get into remission, you may or may not get a little bit of what’s called consolidation chemotherapy, and then go on to a transplant. 

However, sometimes either after the transplant or after chemotherapy before ever getting or instead of ever getting a transplant, there might be ongoing treatment in a lower intensity ongoing basis that is called maintenance.  

So, you’ve got to think about it as induction as what happens first, consolidation is something that happens when you’re in remission, and then maintenance usually refers to ongoing therapy that is different from consolidation. 

It’s usually lower intensity, easier to take, oral types of treatment that may go on and on. And just to be incredibly confusing, it’s different from something like breast cancer, where often the patients are given, “You get six cycles of this, and then you’re done.” From AML, there’s actually often not that type of an obvious plan right out of the gate for the patient. 

The answer will be, “It depends.” It depends. It depends how your treatment looks at this point in time. It depends how you look at this point in time. 

So then, the patients say, “Well, aren’t you going to cure me of this? What are you doing? Aren’t you going to get rid of it?” So, historically, there are some patients who get cured with chemotherapy. They get chemotherapy to get into remission, they get some chemotherapy afterwards, and there’s a cure rate for some patients with that. The majority of patients who are cured with AML get an allotransplant, or a transplant from somebody else. 

Then there’s a whole group of patients where we’re asking the question now, is it possible to get those patients beyond five years – so in oncology, five years is typically defined as cure. Can we get some patients with ongoing therapy to that past-five-year mark without a transplant? That’s in the zone of the ‘coming soon.’ Don’t have a ton of patients in that group right now, but hopefully we will. 

Katherine Banwell:

You’ve mentioned some various treatment types that are used to treat AML. Can you share a brief overview of available treatments? 

Dr. Gail Roboz:

So, the terminology that we use is a little bit annoying, because it is a little bit general. We say intensive and not intensive. 

But historically, intensive chemotherapy referred to a combination of generally two types of agents, cytarabine (Cytosar-U) and an anthracycline, which is a class of chemotherapy, that either just those two together or in combination with sometimes a third or a fourth drug usually keeps people in the hospital for around a month. Not that the chemotherapy takes that long, but the treatment gets rid of basically a lot of cells in the bone marrow, good guys and bad guys, and it takes about three weeks for those normal cells to recover. 

So, a standard intensive induction for AML is often around three to four weeks in the hospital, somewhere between three and five or so days of chemotherapy up front, depending on exactly what the protocol is. The classic regimen is actually still called 3+7, three days of one drug, seven of the other. But there are many variations of that that work. 

The chemo is then stopped, the patient hangs out in the hospital, very frequently getting transfusions and antibiotics, and we wait for the bone marrow to recover.  

Another current path that many patients are getting – almost all older patients, with ‘older’ being defined not by a specific age cutoff, but often 75 and older, almost everybody agrees no longer gets the classic chemotherapy that I just described. At some institutions, that 75 is going down, and even 70 and 65 and above are getting a new type of therapy, mostly because the new type of therapy is working pretty well. That is a combination of something called a hypomethylating agent.  

Drugs like azacitidine (Vidaza, Onureg) or decitabine (Dacogen) in combination with a pill that has changed the landscape of AML more than any other called venetoclax (Venclexta). Venetoclax is a drug that is not exclusively used for AML. 

It actually was originally approved for another type of leukemia. But I think that not many people would argue with the statement that what has changed absolutely the face of AML treatment has been this drug, because it’s a BCL2 inhibitor. What it does is it actually – cancer cells and leukemia cells in particular are very, very good at staying alive.  

They don’t undergo cell death, they don’t want to die, and venetoclax brings down their forcefield so that those cells can actually undergo apoptosis and die. 

Venetoclax in combination with azacitidine or decitabine has transformed the care of the disease, because many patients older than 65 – and the median age of diagnosis of AML is around 68 to 70. So, many patients never were well enough to have the intensive therapy. They weren’t going into remission, and they weren’t having prolonged survival often beyond a few months. 

But now, those patients do actually much better with the combination of aza [azacitidine] and venetoclax. So typically, the induction path is going to be deciding who gets an intensive therapy backbone, usually associated with long hospitalization. Who gets a less intensive backbone – by the way, that is often associated with just the same hospitalization. So, that’s why I don’t love the term ‘low intensity,’ because that implies that it doesn’t work.  

It does, and it also implies that you’re not going to be in the hospital. You probably will, because in the same way as for the more so-called intensive therapies, getting into remission involves getting rid of bone marrow cells and waiting for the normal ones to recover. Even if you are a patient who is getting the venetoclax combined with the azacitidine or decitabine, which is typically called low intensity, you may very well be in the hospital for a month. 

Because depending on where you live and who your family is and how sick you might be, you will probably want us to watch you carefully during that first month, but it’s worth it. Because if you have a good chance of getting into remission, remission is what makes life better and life longer. So, we want to get patients into remission, even if it means upfront time in the hospital. 

Katherine Banwell:

You mentioned one inhibitor as targeted therapy, but there are a couple of others. Would you briefly tell us about those? 

Dr. Gail Roboz:

So, over the years recently, we have identified certain specific targets in AML which are resulting in the addition of medications on these standard backbones. So, the target for venetoclax is something called BCL2, and actually, venetoclax probably makes all chemotherapy better. It’s kind of a controversial statement, but I’m going to stand by it. But in AML, it has been shown that the addition of venetoclax to lots of different backbones makes them work better. There are other things to hit, though.  

For example, there are patients with AML who have something called a FLT3, F-L-T-3 mutation. This mutation also has specific inhibitors that are FDA-approved drugs that target specifically the FLT3 mutation, and if you have one of those, your doctor may add on a FLT3 inhibitor to either a lower intensity or an intensive backbone. Similarly, there are agents called IDH inhibitors. There are IDH1 and IDH2 inhibitors. 

If I start getting into isocitrate dehydrogenase pathways on this webinar, I think everybody will click off, because it’s certainly bored all of the medical students in med school, and it’s pretty tough to understand. But the bottom line is it’s very cool stuff because that boring pathway in medical school that nobody really thought about too much is actually part of very, very, central cellular functions that are a vulnerability now that have been identified in leukemic cells that, if you hit them with these specific inhibitors, patients do better.  

Now, couple of things for patients. It doesn’t mean that it’s better to have a FLT3 or an IDH mutation because the targeted therapies are available. So, a lot of patients are disappointed when they don’t have mutations. I don’t want you to think in that way. It’s not that it’s better, it’s different.  

It identifies a different biology. If you have certain mutations, there are certain medications that may help you more.  

That’s why I think the patients are learning quickly, too, to ask the doc – they may not remember the letters of the alphabet soup, but “Do I have something about my AML that can get one of these targeted therapies added on?” I think is a good question to think about. “Do I have something about my disease that has a specific drug that we’ve already learned makes outcomes better?”  

Katherine Banwell:

There’s a new emerging therapy as well. Is it the menin inhibitor? 

Dr. Gail Roboz:

I think that, in understanding different targets and different pathways, it leads me to a general statement that if you can get yourself potentially onto a clinical trial at an academic center, that is something to consider right out of the gate. Because there is a lot, a lot, a lot going on in this field right now. 

What we are hoping, and the reason that I am talking to you about venetoclax and FLT3 inhibitors and IDH inhibitors, is because of all the patients who jumped onto those clinical trials and proved that those drugs are better. Some of them are my patients! I was fortunate on some of those early trials to have some real winners in patients who got onto the trials. They’re the ones who drove the success. 

So, for example, menin inhibitors, which are very, very exciting, targeted agents for NPM1 and KMT2A mutations and rearrangements – these are complicated to remember as a patient, but there’s a cool drug out there that might be for you. I think that patients who really think about asking the question wherever they are, the “Hey, I just got a diagnosis of AML. Is there a clinical trial that might look good for me?” I think is a great question to ask pretty much out of the gate. 

Katherine Banwell:

The symptoms of AML as well as the side effects of certain medications can vary greatly among patients. So, how do you approach symptom management with your patients? 

Dr. Gail Roboz:

Patients will giggle because I repeat this line. You have to be afraid of the disease, not the treatment. I think that if you read the package insert on a Tylenol, you’re certainly not going  to think you’re going to live for more than 20 minutes if you take one of those. You can certainly appreciate that, with chemotherapy drugs and including some of the novel agents that I’m talking about, if you read package inserts and look at some of the signs and symptoms and things that can happen, it’s extraordinarily overwhelming. 

I think that a lot of what I do for patients is I keep them close. Because if the patient is in the hospital or coming in very frequently in clinic, I think that that everyday assessment of, “What are you experiencing?” and “What can I tell you is the disease’s fault, and what can I tell you is the medication’s fault?” is so, so important. 

Especially in the newly diagnosed patients, where the disease is active. Of course, we want to try to minimize anything that we can do to make the process better for patients, more comfortable for patients, but there are certain things that we do tell people, “You’ve got to slug through this particular problem, because this is the disease’s fault.” This is different from a patient in remission, where they might be getting ongoing therapy with something, or we say, “Hey, wait a minute. You’d be feeling fine, except now you’re taking this medication. How do we minimize messing up quality of life in remission?” 

Because we want you to feel great when you’re in remission. I think the real answer of that is to have a really close collaboration with the healthcare team, and for the patients to really understand – I repeat this because it’s so important. What is the disease’s fault, and what is the treatment’s fault? If there’s something that is therapy-related, do I have a substitute or do I not have a substitute?  

Because if the drug is essential to get us where we need to go, well, what can we do to manage comfort and to manage symptoms until you get to the place where your marrow is working again? 

Katherine Banwell:

That’s great advice, Dr. Roboz. I would like to get to an audience question that we received prior to the program. This one comes from Johanna. “How can I better understand my lab test results? What questions should I be asking my provider about those results?”  

Dr. Gail Roboz:

One of the things that I would say to patients is to be careful when interpreting your own results, because I really am not exaggerating to say that patients have had absolute trauma looking at things that I look at it and say, “Oh, this looks great.” So, the first thing is, be careful being your own doctor. 

The second thing though is that the author of the question has to understand that there’s going to be a tsunami of data coming in with respect to AML treatment. Sometimes in the hospital on a daily basis when you’re in the middle of an induction, there is a true – tsunami is the right word – a deluge of data, and you have to work with your team to say, “What am I following here? What’s important at this phase in my treatment? What’s the number I’m looking at?” Patients sometimes tell me, “I don’t want to know any of this,” and I’m fine with that.  

I think it’s actually okay. Sometimes patients will say, “Give me guidance,” and I will be specific. Because you can actually have a leukemia induction patient where every single laboratory value is abnormal. They might be getting pushed to a device, in the morning, sitting in the hospital on your iPad, 50 abnormal results. You’re trying to battle back the disease and be positive and advocate for yourself, but there are 50 abnormal results in front of you. 

I think you have to really work with the team to say, “What am I looking at today? What are the numbers that are the really important ones? There are 50 abnormal ones here; everything is getting a yellow or a red light in this. How do I go through this?”  

And to appreciate, also, that at different points in the treatment, the beginning of treatment induction post-remission therapy, you’re looking for different things. So, work with your team so that you’re not assessing every single result with equivalent weight, because I think you’re going to stress yourself out.  

Katherine Banwell:

That’s great advice, Dr. Roboz. Thank you. As we close out the program, I’d like to find out what you would like to leave the audience with. Why are you hopeful? 

Dr. Gail Roboz:

AML is changing incredibly rapidly. And  I can tell you it is a lot more fun to be an AML doctor now than it used to be, with respect to what I am offering for patients. We have always fought really, really hard to have our wins, but we’re winning more. I do think that it is a complicated space to navigate for patients, but there is room for a lot of optimism. 

I think we are getting patients transplanted  –  patients that we never thought would ever go through a transplant or getting transplanted. Patients who never had a chance of even living more than six or eight months or living much longer than that. Is it perfect? No. Do we have as many cures as we want?  

No, but there’s a lot going on. I think if patients feel that excitement, they will also feel the need to ask about those clinical trials. Because I think that for a lot of patients, clinical trials is an area where they would be worried. They’re not sure that they want to. “I don’t want to be a guinea pig,” and yet here I can say in the AML space, one after another after another drug approvals in the last several years, with the patients on those trials being awfully happy that they participated. 

So, I think that it’s a very, very terrifying diagnosis. There’s nothing that I can do to take the sting out of that. But try to find yourself in an optimistic place with options that are being offered to the very, very, very best that we can do. There are patients who are listening, I’m sure, who have relapsed or refractory disease who are not feeling that optimism. 

I want to address you specifically, because we don’t have enough yet. We’re trying. When you have AML that has come back or come back multiply, that’s dangerous and difficult. But for those patients in particular, try really hard to get onto clinical trials. If the drugs that we have out there – if you’ve already taken them and they haven’t worked for you or if they’re not serving you well, if you’re in good shape and the drugs that we have aren’t good enough, well, let’s see if we can get you on something that’s investigational. 

Katherine Banwell:

Dr. Roboz, thank you so much for taking the time to join us today. 

Dr. Gail Roboz:

Thank you for having me. 

Katherine Banwell:

I also want to thank all of our collaborators. To learn more about AML and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us today.  

What Is the AGILE Study? Research for AML Patients With the IDH1 Mutation

What Is the AGILE Study? Research for AML Patients With the IDH1 Mutation from Patient Empowerment Network on Vimeo.

AML expert Dr. Omer Jamy reviews the results of the AGILE study, a clinical trial evaluating the efficacy and safety of ivosidenib + azacitidine vs placebo + azacitidine in patients with previously untreated AML with an IDH1 mutation.

Dr. Omer Jamy is a Leukemia and Bone Marrow Transplant Physician and Assistant Professor at the University of Alabama at Birmingham. Learn more about Dr. Omer Jamy.

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Advances in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia (AML)

Advances in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia (AML)

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Essential Testing | Optimizing AML Care With Personalized Medicine

Essential Testing Optimizing AML Care with Personalized Medicine

Transcript:

Katherine Banwell:

Dr. Jamy, data was presented at ASCO from the agile study. What is the study and what does the news mean for AML patients? 

Dr. Omer Jamy:

Yes, thank you. So, the AGILE study is basically a randomized Phase III study. It is specifically for patients with AML who harbor an IDH1 or isocitrate dehydrogenase 1 mutation. Now IDH1 mutation is thought to be rare.   

It occurs in around six to 12 percent of patients with acute myeloid leukemia. So, a few years ago there was a drug approved by the FDA to treat patients in the relapsed or refractory setting with an IDH1 mutation. And that drug is called ivosidenib (Tibsovo). And this drug is also approved for elderly patients ineligible for intensive chemotherapy but it was mainly initially approved for the relapsed/refractory setting.  

So, all of these drugs when they initially get approved – so this is targeted therapy. It’s targeting IDH1 mutant AMLs, so patients with AML without an IDH mutation will not benefit from such a drug. So, when you find targeted therapy, the general workflow is it gets tested in the later settings. If it looks promising, then people try to bring it in the upfront settings. So, this was a Phase III study of newly diagnosed acute myeloid leukemia patients harboring an IDH mutation.  

And it randomized them to a combination of azacitidine plus ivosidenib versus azacitidine plus placebo.  

When the study was started, the standard of care for patients ineligible to receive intensive chemotherapy was azacitidine (Vidaza). So, this study again, just to highlight, focused on patients who were not ineligible for intensive chemotherapy. So, these may be patients who were either above the age of 75 or below the age of 75 but had comorbidities which would have prevented them from receiving intensive chemotherapy. These comorbidities could be any organ dysfunction such as the heart, kidneys, liver, lung, or poor performance status. So, the primary endpoint of the study was event free survival. And the primary endpoint of the study was met with a hazard ratio of .33 in favor of the combination of azacitidine  and ivosidenib. The study also showed that overall survival was improved in patients getting the combination compared to patients just getting azacitidine and placebo.  

Which was roughly around 20 to 24 months versus eight months for the placebo and azacitidine arm. And then obviously when you combine drugs you want to make sure that by adding two drugs, you’re not causing more toxicity. So, the toxicity profile between the two arms was similar actually. They saw less infections and neutropenia in the ivosidenib and azacitidine arm compared to azacitidine alone. So, that was basically the AGILE study where they looked at patients with IDH mutant acute myeloid leukemia.  

How Can You Thrive With AML? Advice for Navigating Care.

How Can You Thrive With AML? Advice for Navigating Care. from Patient Empowerment Network on Vimeo.

How can you thrive with AML? In this animated explainer video, an AML specialist and patient discuss how to make informed decisions about your care and live a full life with AML.

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Transcript:

Raquel: 

Hi, I’m Raquel. Nice to meet you! I am living with acute myeloid leukemia, or AML. When I was first diagnosed, my husband and I were very overwhelmed by a cancer diagnosis. But once I found the right care team and learned more about my disease and treatment options, I’ve been living a full life.   

Meet, Dr. Shaw – my doctor. 

Dr. Shaw: 

Hi! I’m Dr. Shaw, and I’m a hematologist specializing in the care of people with AML.   

AML is a cancer of the blood and bone marrow, and it is the most common acute leukemia in adults in the United States. Because this is an acute leukemia, it progresses quickly and should be treated immediately.   

There are typically two phases of therapy:  

  • Induction therapy is the first line of treatment and is meant to induce remission.  
  • The second phase is consolidation therapy which is meant to maintain the remission.  

As Raquel mentioned, with the right team and care plan, it is possible to live a full life and to thrive with AML. 

Raquel: 

It’s so true. Navigating my care has been much easier, because I partner with my healthcare team – it makes me feel involved and confident in decisions. 

Dr. Shaw: 

That’s right, Raquel. When considering treatment, it’s important to weigh all of your options.  

While your healthcare team is the expert when it comes to the clinical side of your disease, you, as the patient, are the expert on how treatment will impact YOU and your lifestyle.  

Raquel: 

And as someone who knows my needs well, my husband is another key member of my team.  He comes with me to appointments and takes notes during visits, and when it is time to make decisions about my care, we both feel well-informed about the options. 

So, Dr. Shaw – what factors should be considered when choosing an AML treatment? 

Dr. Shaw: 

Well, it’s important to note that everyone’s AML is different, so what may work for one person may not work for another. In general, we consider certain factors, such as: 

  • The patient’s age and overall health. 
  • Any pre-existing health issues. 
  • Test results, including any mutational testing results. 
  • Finally, and most importantly, the patient’s treatment goals and preference. 

Raquel: 

And I like to make informed decisions. So, when considering therapy, I also did some research on my own, and then discussed the information with my healthcare team. It helped my husband and me understand what we’d learned, and confirmed our decision. 

Dr. Shaw, what sort of questions should patients ask their doctor when considering a treatment plan? 

Dr. Shaw: 

Great question. When choosing therapy, patients should ask: 

  • How is the treatment administered, and how often will I need treatment? 
  • What are the potential side effects of the treatment? 
  • How will the effectiveness of the treatment be monitored? 
  • And, what are options if this treatment doesn’t work for me? 
  • Is there a clinical trial that might be right for me? 

Raquel: 

That’s great advice. Once you’ve begun treatment, it’s important to continue to share how you are feeling with your healthcare team – be sure to mention any side effects or symptoms you may be having. 

Dr. Shaw: 

That’s right, Raquel. If you speak up about what’s bothering you, we can usually find a way to manage the issue. 

It’s also important point to tell your doctor if you’ve missed a dose of your medication. Many of the newer AML therapies are self-administered, and it’s important to let us know so we can adjust the plan if necessary. 

So, Raquel, can you share advice for thriving with AML?  

Raquel: 

  • First, understand and participate in treatment decisions. Be sure to educate yourself about AML and share your personal preferences when choosing therapy. 
  • Then, communicate regularly with your healthcare team – don’t wait to share information only when you have an appointment.  
  • And, utilize your whole team – nurses, nurse practitioners, and others, are all there to help you. 
  • Use your patient portal. You can view lab work and test results, or even use the messaging feature to communicate with your team. 
  • Bring a friend or loved one to appointments and always write down any questions or concerns in advance. 

Dr. Shaw: 

And, most importantly, remember you are at the center of your care. Advocate for yourself! 

To learn more, visit powerfulpatients.org/AML to access a library of tools. Thanks for joining us! 

AML Treatment Approaches | Factors That Impact Options

AML Treatment Approaches | Factors That Impact Options from Patient Empowerment Network on Vimeo.

What factors are considered when choosing an AML treatment approach? Dr. Ann-Kathrin Eisfeld explains how shared decision-making comes into play when deciding on a therapy and reviews the options available to treat AML.

Dr. Ann-Kathrin Eisfeld is Director of the Clara D. Bloomfield Center for Leukemia Outcomes Research at The Ohio State University and a member of the Leukemia Research Program at the OSUCCC – James. Learn more about Dr. Eisfeld.

See More From INSIST! AML

Related Resources:

Essential Testing | Optimizing AML Care With Personalized Medicine

How Have Advances in Testing Impacted AML Care

AML Targeted Therapy: How Molecular Test Results Impact Treatment Options

Transcript:

Katherine Banwell:

With all the new tools that are available, what other factors do you consider when working with an AML patient to choose a treatment approach for them?  

Dr. Eisfeld:

The most important aspects are what we call – and this is – I’m glad that you bring this question up because I feel you have to think of – and that was what we’ve been talking about – called disease-associated factors. This is everything in the leukemic cell. They – how does a leukemia looks like? How does the blast look like? What changes are there?  

That’s the biggest part of what I would call patient-associated factors: the patient age, the patient performance status, actually the patient. In every – because I think, sometimes, we forget about it. But we just look at all the molecular testing.  

But even if – for example, there would be a patient with a very good risk leukemia, where I think, “Oh, this leukemia should respond very well to an intensive chemotherapy.” 

If the patient cannot tolerate chemotherapy or – and I see it more often than I would wish for patients who are young who have a great performance status, but they just cannot – they – their family reasons. Small children sometimes – they just cannot be away for so long. This all comes into consideration. So, it’s really important because we all work together as a team. And the right treatment for the leukemia might not be the right treatment for the patient.  

And for most cases, however, I think, it will only work if one stands with a whole heart with both physicians, and patients, and family. Because it’s a long journey behind the care that’s being given. And so, this is a joint decision-making, and there are different options that can be done. Of course, I would not advise something where I would think there are no chances of success.  

And so, this has to be an open discussion. But this is – it’s very often a very tough treatment to communicate that and see what are the goals of each patient? That will be most important for treatment and decision-making.     

Katherine Banwell:

What types of AML treatment classes are currently available?  

Dr. Eisfeld:

This is a very good question. The most classic treatment class is intensive chemotherapy. This is just because people might have heard the names. It is called 3 + 7 or 7 + 3, which refers to one weeklong impatient chemotherapy treatment. But you get one chemotherapy for seven days. And the first three days, you get a second treatment as well.  

That’s why it’s called three in seven in here, but it’s a total of seven days. So, we have intensive chemotherapy. And there are different flavors of it. But this is usually the backbone. The second class is what I would call a targeted inhibitor. And here we can look at two different aspects. We have targeted inhibitors for a specific DNA mutation that are found. And specifically, one are called IDH or FLT3 mutations.  

And these are pill forms that I usually by now combined with a third drop class which is called hypomethylating agents. And I will go through in a moment.  

But these are pills that really only work in patients and carry that genetic change. They have very, very low toxicity and very high chances of working. So, that’s why this testing is so important to see if one is one of the 15 percent of AML patients carrying an IDH mutation – 15 percent isn’t low. And a similar rate carries a FLT3 mutation.  

And then there is also going to target inhibitors. That is targeted because it is against what I would call a pathway. The gene that is commonly activated in acute leukemia – and this is called BCL-2 and the drug is called venetoclax (Venclexta).  

This is now stormed through the acute myeloid leukemia world in just a few years ago and has been approved as a front-line treatment option for several patients, especially for those who are older. And we know that even patients who respond usually favorably to chemotherapy, some of those also respond well to venetoclax the Bcl-2 inhibitor. The benefit is that this treatment in many cases if it works, can be done as an outpatient in here and has very often lower complications.  

It is actually has so good results that I – sometimes it seems too easy. So, we actually advise patients to still try to get – the first time they get the treatment, do it at a center where it’s done more commonly. Because it sometimes – don’t underestimated the power of a pill. And it’s still a very, very powerful drug. So, doing it in a controlled setting – because if cancer cells break down, they break down and can create all sorts of trouble.  

So, that is really something – for several leukemias, it can be concerning. And again, now the treatment group would be called hypomethylating agents. The names are azacitidine (Vidaza) and decitabine (Dacogen). And they act in a very different way. They try to change the epigenetics like methylation patterns. And often, if it is an untargeted way of the tumor cells and they can be used alone.  

Or very often by now in combination with the targeted inhibitors that I was just mentioning. These are infusions that can be done either over five, seven, or 10 days depending on the combination treatment. And for patients, as I mentioned before, that don’t respond well to many other options to those patients with a complex karyotype. This is, for example, a scenario where patients can just receive this as their only therapy.          

Katherine Banwell:

What about stem cell transplant? You didn’t mention that.   

Dr. Eisfeld:

Yes. That would be the next one. So, stem cell transplant always comes as an option, which I would call as a maintenance therapy. Again, two aspects. We have two different end goals.  

First is get rid of some leukemia. Second is to make sure it stays away. And as soon as the leukemia is in complete remission, depending on the performance status – the agent. Again, in multiple different things. It’s not an easy decision. 

At that time, there has to be a conversation. And that always involves a leukemia physician and a transplant physician very often. These are different providers that goes for the risks and benefits. Where the question is if I only continue to do chemotherapy – because it’s never only once. You would always have to repeat your chemotherapy. What is the likelihood that the leukemia comes back, and does it outweigh the risks that comes with the stem cell or bone marrow transplant that comes in here. But for many leukemias, especially for young patients and for patients with higher risks, this is the only chance of a cure. That is the most curative and only curative attempt for many leukemia attempts.  

Katherine Banwell:

Where do clinical trials fit into the treatment plan? 

Dr. Eisfeld:

That is the absolute backbone. We always have to think about that. 

Everything – all the treatment options that I mentioned – have been clinical trials, just very, very short time – very few years ago. So, every patient that comes to a leukemia or a cancer center, clinical trials will be discussed if they’re available. Because they will provide a special opportunity to have even more fine-tuned treatments – either newer agents. And I think what is very important to mention is that all clinical trials that are available would give the option of the best standard of care.  

And then the hope that a patient wouldn’t be getting any of the best standard of care options that are approved. The hope is that the new agent or added agent in many cases would even do better.  

It’s also important that there’s a lot of additional monitoring during the trial. I think it can be seen in two ways as two parts of a coin. In one way, it may be additional visits to the hospital or additional blood draws that are necessary to be sure that the medications are safe, and that researchers and conditions can learn about it. But on the other hand, it also gives you this extra bit of being looked after and really getting checked in and out, making sure that all organs are functioning that everything is just going fine. And many patients appreciate this a lot. And they have this pair of extra eyes on them all the time.  

Katherine Banwell:

Dr. Eisfeld, what therapies are available for AML patients who relapse or don’t respond to initial therapy? And is this treatment approach different from those who are newly diagnosed?  

Dr. Eisfeld:

Most of the time, the treatments available at relapse are the same available at the first diagnosis. Just because we know now that, for example, if you have a molecular marker that, for example, is available, it would act with also relatively high chance of relapse upset. However, at relapse, the most important thing I personally would do is consider a clinical trial even stronger than in the first mindset. 

 Because it means that the leukemia outsmarted current treatments very often. So, usually what we would be doing is see if there is a targeted inhibitor or a cell mutation FLT3 or IDH, which I would personally always prefer to go in MLL rearrangement now for the new menin inhibitors where one would go with the same option as if it would have been their diagnosis. But if not to really consider clinical trials is a strong urge. 

Katherine Banwell:

Should patients or should relapsed patients undergo genetic testing again? Is it necessary?  

Dr. Eisfeld:

Yes. At any time. Yes. Because we know that the leukemia changes. And you just can think about it in the way is that the cells that are surviving treatment, they’ve become smart. There was so much poison. There was so much treatment put on them. 

And the ones that survive might have a quiet additional chromosome change as additional gene changes. And even if a genetic change has not been present at time of diagnosis, the reason the cell has survived might have been that it has now one of these changes that came up on a later time during treatment or while the cell is hiding somewhere to come back. 

Expert Advice for Navigating AML Treatment and Care Decisions

Expert Advice for Navigating AML Treatment and Care Decisions from Patient Empowerment Network on Vimeo.

AML expert Dr. Ann-Kathrin Eisfeld reviews the importance of essential testing and explains how the results may impact the care and treatment of patients with AML. Dr. Eisfeld also shares updates on new and developing AML research.

Dr. Ann-Kathrin Eisfeld is Director of the Clara D. Bloomfield Center for Leukemia Outcomes Research at The Ohio State University and a member of the Leukemia Research Program at the OSUCCC – James. Learn more about Dr. Eisfeld.

See More From INSIST! AML

Download Resource Guide

Related Resources:

How Does the Presence of Molecular Markers Affect AML Care

Does Maintenance Therapy Have a Role in AML Care

Advances in AML Research _ Where Do Clinical Trials Fit In

Transcript:

Katherine Banwell:

Hello and welcome. I’m Katherine Banwell, your host for today’s webinar. Today’s program is a part of our Insist series. We’ll discuss how to access the most personalized AML therapy for your individual disease and why it’s vital to insist on key testing. Before we meet our guest, let’s review a few important details 

The reminder email you received about this program contains a link to a program resource guide. If you haven’t already, click that link to access information to follow along during the webinar. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining me is Dr. Ann-Kathrin Eisfeld. Dr. Eisfeld, welcome. Would you please introduce yourself?  

Dr. Eisfeld:

Hi, thank you so much, Kathrine. Yes. My name is Ann-Kathrin Eisfeld. I’m currently an assistant professor and hematologist at the Ohio State University. 

And I’m also serving as the director of the Clara D. Bloomfield Center for leukemia outcomes research at the James. 

Katherine Banwell:

Thank you so much for joining us today and taking the time to discuss this important issue. To set the stage for today’s discussion, Let’s start with this important question. How would you define personalized medicine as it relates to AML care? 

Dr. Eisfeld:

I define personalized medicine in AML as have a complete testing at time of diagnosis that consists of not only the morphology of the bone marrow, but we call immunophenotyping, which is looking at the surface markers, but also full review of all the chromosomes, which is called cytogenetics. And with those metaphase testing, I’m looking really at all of them and at the hot spots, which is done by a technique called FISH 

And then most importantly, for personalized testing, it also needs to consist of testing the most common, recurrent gene mutations. Changes in the tumor DNA that we know are contributing to the disease biology and also to the response of the leukemia to different genes.   

Katherine Banwell:

Thank you for that, Dr. Eisfield. That helps guide us as we begin our conversation.  

I imagine that personalizing therapy for a patient requires a number of tests and then thorough review of the test results. Could you provide an overview of the tests necessary to help understand a patient’s specific AML? 

Dr. Eisfeld:

Yes. Absolutely. There are multiple things that go in. And let me –even before we go into the tests – point out one thing. Because as we talk about individualized care – and it is also important to keep in mind that it will be also dependent on the age and of the performance status of the patient. 

Because we know that all the changes that are going to be reviewed might be more or less severe depending on really the age of the patient we are discussing. The most critical aspect for every AML patient is a bone marrow biopsy and a bone marrow aspirate on which the testing that I have been referring to are performed.  

One, it gives us information about how the – after review of the hematologist, it gives us information about the specific kind of the leukemic cell.  

And very importantly – and this is a very more recent development that we know about that’s important. It also tells us whether the acute leukemia is really happening as an acute leukemia or whether the patient without knowing it before might have had a precursor issue. And this is something that by now really in just about half a year we can use in addition to direct treatment.  

So, it seems like an ancient thing that we think that the microscopic review is important. But that is one part of it.  

The second part – and this is, again, all based on the bone marrow biopsy. The inspection of chromosomes, as I mentioned, may be called cytogenetics. This test takes longer. It sometimes takes up to two weeks to result. And similar, looking at the tumor DNAs and mutations that is done either if you’re at a large institution such as Ohio State or other cancer centers. It’s done in house. Whereas at smaller institutions, it would be done by a sent-out testing that has these recommended gene mutation testings done. And some of those result just within a couple of days.   

And these are – but we can talk. And I know we are going to talk a little bit more about it later, but we now have targeted therapies available. This is a really super exciting topic we couldn’t have talked about just even five years ago. And those mutations and those DNA changes come back usually within three to five days.  

So, that we are able to decide on treatment. 

Katherine Banwell:

How can someone ensure they’re getting an accurate diagnosis? 

Dr. Eisfeld:

That’s a very good question. I think the most important part is to go to somebody who has seen acute leukemias as a living. It is a very rare cancer as you know. And if you are seen even by a general oncologist who might be a fantastic oncologist, he might just see one or two cases per year. And thus, might not be up-to-date on the newest recommendations. So, I can just advise anybody – even if he lives further away and trusts his physician a lot – to – for the diagnosis and for treatment planning, come to a comprehensive cancer center, at least for a therapy planning. Because what is now possible is many of these treatments is that we can just give advice.   

And then you can still receive treatment in some cases really back at home. But be sure the testing was done correctly. And really give you every option to take into consideration what the best treatment would be for you, what the best treatment is for the patient. Having this trip – which can be hours of a drive. And I appreciate this. Having that done once would be, I think, the best thing to do.  

Katherine Banwell:

Many cancer types are typically staged. But that’s not the case with AML. AML is often considered low risk or high risk. Is that right? 

Dr. Eisfeld:

Yes. And we – I think that’s very well how you put it. And we can even – they even add an intermediate risk by now to it. And I love this question because that’s what I like to study or what I’m studying here. The one important thing to keep in mind – and this is something even many hematologists don’t think about is that the risk assignment of acute leukemia, of AML if you think about it as low, or high, or intermediate risk is risk – or is actually better said not risk, but chances to respond to conventional chemotherapy. So, the way all this was defined is that if you have, for example, a multitude of chromosomal abnormalities – as you call it complex karyotypes – it would be considered adverse. This means your chances of responding to the standard of care in terms of chemotherapy are very, very low.   

And similarly, if you have other changes such as a NPM1 mutation, your chances are considered very high. And but – so, the risk assignment with the increase of treatments now changes. We still also – and when I look at that, I think about it in the same way. But in my mind, if I’m talking to a patient, I’m trying to make sure to say, this is considered an intermediate or adverse risk.  

But this means that I would not, at the first place, consider you for a standard chemotherapy but rather advise you to participate in a clinical trial or have an alternative care. The second implication especially for younger patients would be to – if you’re intermediate or adverse risk, that you would routinely be considered for bone marrow transplant or stem cell transplant.       

Katherine Banwell:

Okay. So, what does it mean to be high risk then?  

Dr. Eisfeld:

It means that your likelihood of going into remission – the standard of care is very low. This means – I mean, in very practical numbers, it might be as low as 20 or 30 percent. This meaning getting the leukemia into remission, there are very important differences. The first step at every time in the same high risk means if the patient receives the treatment, how high are the chances that we can get rid of the leukemia? 

The second question is how high are the chances once it’s gone that it stays away? Or how high are the chances of relapse? In adverse risk most cases, it’s both – a combination of those. The chances of going into complete remission are lower and the chances of it coming back are higher. So, we have to be very aggressive. This means that we have to consider alternative treatment options. And even if we are then lucky and achieve remission, that we might have to move to more intensive additional treatments such as a bone marrow transplant.    

Katherine Banwell:

Dr. Eisfeld, the landscape of AML has changed significantly in recent years. How have advances in testing improved patient care?  

Dr. Eisfeld:

It is a different world, Katherine, honestly. I mean, I started practicing in hematology in taking care of AML patients back in Germany actually in the year 2007. 

Back then, there was no other testing that was available. All we were guiding and all that we had available was morphology and cytogenetics. And very often, it was very inaccurate. And we also only had two treatment kinds available. One was intensive chemotherapy, and one was something that was just a little bit better than best supportive care. So, many patients could not receive treatment. And the increase in knowledge that we have on a molecular level in AML really did two things at once.  On one, we understood we had a more fine tuned understanding on which patients would respond. And the second thing is that this knowledge about the molecular landscape enabled us to have new treatments available that are sometimes in pill form that can target specific mutations in patients who carry these genetic changes.   

Katherine Banwell:

Should all AML patients undergo in-depth testing like biomarker testing or cytogenetics? 

Dr. Eisfeld:

Yes. Every patient should do that. It can make the difference between life and death. And it can make the difference between receiving – having a hospital stay of four weeks with intensive chemotherapy versus taking the pill at home. This is very rare that this is possible. But it is possible. And of course, you – one would not want to miss this chance if it would be possible.   

Katherine Banwell:

With all the new tools that are available, what other factors do you consider when working with an AML patient to choose a treatment approach for them? 

Dr. Eisfeld:

The most important aspects are what we call – and this is – I’m glad that you bring this question up because I feel you have to think of – and that was what we’ve been talking about – called disease-associated factors. This is everything in the leukemic cell. They – how does a leukemia looks like? How does the blast look like? What changes are there?  

That’s the biggest part of what I would call patient-associated factors: the patient age, the patient performance status, actually the patient. In every – because I think, sometimes, we forget about it. But we just look at all the molecular testing.  

But even if – for example, there would be a patient with a very good risk leukemia, where I think, “Oh, this leukemia should respond very well to an intensive chemotherapy.” 

If the patient cannot tolerate chemotherapy or – and I see it more often than I would wish for patients who are young who have a great performance status, but they just cannot – they – their family reasons. Small children sometimes – they just cannot be away for so long. This all comes into consideration. So, it’s really important because we all work together as a team. And the right treatment for the leukemia might not be the right treatment for the patient.   

And for most cases, however, I think, it will only work if one stands with a whole heart with those physicians, and patients, and family. Because it’s a long journey behind the care that’s being given. And so, this is a joint decision-making, and there are different options that can be done. Of course, I would not advise something where I would think there are no chances of success.  

And so, this has to be an open discussion. But this is – it’s very often a very tough treatment to communicate that and see what are the goals of each patient? That will be most important for treatment and decision-making.     

Kathrine Banwell:

Dr. Eisfeld, we’ve been discussing treatment choices and how they vary for individual patients. What types of AML treatment classes are currently available? 

Dr. Eisfeld:

This is a very good question. The most classic treatment class is intensive chemotherapy. This is just because people might have heard the names. It is called 3 + 7 or 7 + 3, which refers to one weeklong impatient chemotherapy treatment. But you get one chemotherapy for seven days. And the first three days, you get a second treatment as well.  

That’s why it’s called three in seven in here, but it’s a total of seven days. So, we have intensive chemotherapy. And there are different flavors of it. But this is usually the backbone. The second class is what I would call a targeted inhibitor. And here we can look at two different aspects. We have target inhibitors for a specific DNA mutation that are found. And specifically, one are called IDH or FLT3 mutations.  

And these are pill forms that I usually by now combined with a third drop class which is called hypomethylating agents. And I will go through in a moment.  

But these are pills that really only work in patients and carry that genetic change. They have very, very low toxicity and very high chances of working. So, that’s why this testing is so important to see if one is one of the 15 percent of AML patients carrying an IDH mutation – 15 percent isn’t low. And a similar rate carries a FLT3 mutation.  

And then there is also going to target inhibitors. That is targeted because it is against what I would call a pathway. The gene that is commonly activated in acute leukemia – and this is called BCL-2 and the drug is called venetoclax (Venclexta).  

This is now stormed through the acute myeloid leukemia world in just a few years ago and has been approved as a front-line treatment option for several patients, especially for those who are older. And we know that even patients who respond usually favorably to chemotherapy, some of those also respond well to venetoclax the Bcl-2 inhibitor. The benefit is that this treatment in many cases if it works, can be done as an outpatient in here and has very often lower complications.  

It is actually has so good results that I – sometimes it seems too easy. So, we actually advise patients to still try to get – the first time they get the treatment, do it at a center where it’s done more commonly. Because it sometimes – don’t underestimated the power of a pill. And it’s still a very, very powerful drug. So, doing it in a controlled setting – because if cancer cells break down, they break down and can create all sorts of trouble.  

So, that is really something – for several leukemias, it can be concerning. And again, now the treatment group would be called hypomethylating agents. The names are azacitidine (Vidaza) and decitabine (Dacogen). And they act in a very different way. They try to change the epigenetics like methylation patterns. And often, if it is an untargeted way of the tumor cells and they can be used alone.  

Or very often by now in combination with the targeted inhibitors that I was just mentioning. These are infusions that can be done either over five, seven, or 10 days depending on the combination treatment. And for patients, as I mentioned before, that don’t respond well to many other options to those patients with a complex karyotype. This is, for example, a scenario where patients can just receive this as their only therapy.          

Katherine Banwell:

What about stem cell transplant? You didn’t mention that.  

Dr. Eisfeld:

Yes. That would be the next one. So, stem cell transplant always comes as an option, which I would call as a maintenance therapy. Again, two aspects. We have two different end goals.  

First is get rid of some leukemia. Second is to make sure it stays away. And as soon as the leukemia is in complete remission, depending on the performance status – the agent. Again, in multiple different things. It’s not an easy decision. 

At that time, there has to be a conversation. And that always involves a leukemia physician and a transplant physician very often. These are different providers that goes for the risks and benefits. Where the question is if I only continue to do chemotherapy – because it’s never only once. You would always have to repeat your chemotherapy. What is the likelihood that the leukemia comes back, and does it outweigh the risks that comes with the stem cell or bone marrow transplant that comes in here. But for many leukemias, especially for young patients and for patients with higher risks, this is the only chance of a cure. That is the most curative and only curative attempt for many leukemia attempts.  

Katherine Banwell:

Where do clinical trials fit into the treatment plan? 

Dr. Eisfeld:

That is the absolute backbone. We always have to think about that. 

Everything – all the treatment options that I mentioned – have been clinical trials, just very, very short time – very few years ago. So, every patient that comes to a leukemia or a cancer center, clinical trials will be discussed if they’re available. Because they will provide a special opportunity to have even more fine-tuned treatments – either newer agents. And I think what is very important to mention is that all clinical trials that are available would give the option of the best standard of care. And then the hope that a patient wouldn’t be getting any of the best standard of care options that are approved. The hope is that the new agent or added agent in many cases would even do better.  

It’s also important that there’s a lot of additional monitoring during the trial. I think it can be seen in two ways as two parts of a coin. In one way, it may be additional visits to the hospital or additional blood draws that are necessary to be sure that the medications are safe, and that researchers and conditions can learn about it. But on the other hand, it also gives you this extra bit of being looked after and really getting checked in and out, making sure that all organs are functioning that everything is just going fine. And many patients appreciate this a lot. And they have this pair of extra eyes on them all the time.  

Katherine Banwell:

Dr. Eisfeld, what therapies are available for AML patients who relapse or don’t respond to initial therapy? And is this treatment approach different from those who are newly diagnosed?   

Dr. Eisfeld:

Most of the time, the treatments available at relapse are the same available at the first diagnosis. Just because we know now that, for example, if you have a molecular marker that, for example, is available, it would act with also relatively high chance of relapse upset. However, at relapse, the most important thing I personally would do is consider a clinical trial even stronger than in the first mindset. 

Because it means that the leukemia outsmarted current treatments very often. So, usually what we would be doing is see if there is a targeted inhibitor or a cell mutation FLT3 or IDH, which I would personally always prefer to go in MLL rearrangement now for the new menin inhibitors where one would go with the same option as if it would have been their diagnosis. But if not to really consider clinical trials is a strong urge. 

Katherine Banwell:

Should patients or should relapse patients undergo genetic testing again? Is it necessary?  

Dr. Eisfeld:

Yes. At any time. Yes. Because we know that the leukemia changes. And you just can think about it in the way is that the cells that are surviving treatment, they’ve become smart. There was so much poison. There was so much treatment put on them. 

And the ones that survive might have a quiet additional chromosome change as additional gene changes. And even if a genetic change has not been present at time of diagnosis, the reason the cell has survived might have been that it has now one of these changes that came up on a later time during treatment or while the cell is hiding somewhere to come back.  

Katherine Banwell:

Are there therapies in development that are showing promise for patients with AML? 

Dr. Eisfeld:

There are so many of those. It’s hard to count. And this makes me very happy. There are exciting and again, targeted drugs.  

Once drug class is called menin inhibitors, which we – which were just published that show high promise.  

And again, very difficult to treat several groups of patients who harbor chromosome changes in MLL genes in here. So, that is a very exciting option.  

And there’s very exciting treatments with respect to what you call antibodies – monoclonal antibodies that protects the surface proteins that are being checked regularly. And one of those, for example, is called magrolimab. And that has even promise in these high-risk leukemias or adverse risk leukemias.  

And then we are not there yet, but I’m sure we will be in the not too near future. There are also multiple trials that are looking at what we call CAR-T cells. But patients might have heard about for lymphomas or acute lymphoblastic leukemias. AML is a little more tricky with respect to those. 

But we’ve seen pre-clinical studies that look really exciting. And I think it’s just going to be just a little more fine-tuning to make those easier, available, and more targeted for AML patients. And I’m very much looking forward to seeing those come more onto the market.      

Katherine Banwell:

You mentioned the new menin inhibitors. Who are they right for?   

Dr. Eisfeld:

We try to find out more, but definitely for patients that have been shown to be beneficial for patients who have chromosomal and rearrangements of the MLL gene or KMT2A gene. And there’s also good data on patients who have NPM1 mutations.  

Even though we know – and these are mutations who harbor this kind of genetic change – have now a plethora, which is a great, of treatment options.

Because we know even conventional chemotherapy has been working decently well in them. We know that venetoclax also is supposed to work very well in them. But again, the data on the menin inhibitor with respect to NPM1 mutations is very exciting. 

Katherine Banwell:

So, Dr. Eisfeld, we’ve covered a lot of information related to AML care. As a researcher, what other topics are currently top of mind for you in the field of AML? What are you passionate about? 

Dr. Eisfeld:

Again, so many parts. I think there are probably three main things that I’d like to name. And I think about it as a little bit outside the box. Most of what we know about AML, we have become so much better. It’s because we have been studying patients who were treated over the past decades on clinical trials and very often here in the U.S. or in Europe.  

 But all clinical trials have a bias in that most of them have been done A) on patients who are younger than the age of 60. And B) fewer patients of other races and ethnicities included. And had patients not included that have AML, for example, not only in the bone marrow but on extramedullary sites – how we call it – up to 10 percent of their patients. And also, very often have not been done on very old patients where the AML is very common. So, all the patients – patients from other race, ethnicities, or underrepresented minorities, and patients who present with extramedullary disease are currently in my – underserved.  

And these are exciting areas and opportunities of research and of active clinical practice. Because those are the patients we need to include if it’s possible now to include them in clinical trials. 

If there are no trials available, then make sure any other additional molecular testing it done to understand them better and to advance our disease knowledge that we make sure that we can give the best possible care.  

Katherine Banwell:

I think that the most important part is to get the molecular testing, and to enroll into clinical trials, and then to very often biobanking 

Why am I saying that is because our knowledge AML comes from patients who donated some tissue so that we could learn – researchers decades ago could learn about the genes. We know that leukemias differ so much in between patients.  

So, I am worried that we are yet missing out on potentially important genes that need to be discovered and where we could develop docs for. This will only be possible with these additional testing. 

 The second part is to really consider going to larger treatment and larger treatment cancer center. And there are support systems in case that can help in here.  

And the third part is to get involved even as early as possible even if you’re not personally affected, with Be The Match – with bone marrow transplant because there’s a paucity of donors, of people of color that makes it harder for these patients to get a potentially curative treatment in here.  

We have other options now in bone marrow transplant where one can use only half-matching donors and or other availabilities. But again, that doesn’t outweigh that the bone marrow and donor registry that we need to get better at.  

And I can – there are just so many factors – such a high degree of structural racism that affects people from every corner. And I think we as physicians, as society, and everybody need to acknowledge that. And we have to make sure that we get better to, again, give every patient the best care and keep the patient in mind and see what’s right for them at the right moment.    

Katherine Banwell:

Where can patients or people who are interested find out about being a donor? 

Dr. Eisfeld:

There is the website called “Be the Match” that one can put in. This is probably the best way to get first information.   

And usually, at all the cancer sites. And sometimes, there is information at lab donation places, universities, either or the American Red Cross.  

Usually those places have information laid out there as well.    

Katherine Banwell:

Dr. Eisfeld, before we close, I’d like to get your thoughts on where we stand with progress in the field of AML. What would you like to leave the audience with? Are you hopeful? 

Dr. Eisfeld:

I am incredibly hopeful. I hope – when I started working in hematology, as I said at that time, it was just about when imatinib (Gleevec) came out. Which is this CML pill that really revolutionized care. And so, at that time, I would be – all patients on that bone marrow transplant service had chronic myeloid leukemia. And because they all had to undergo bone marrow transplant. Then Gleevec came, and today, there are no such patients who are see or very rarely that require such intensive care.  

So, I am very hopeful that in my practice time, which hopefully –and even earlier on – that there will be a time where we find targeted therapies for almost all patients.  

Katherine Banwell:

Dr. Eisfeld, thank you so much for joining us today. 

Dr. Eisfeld:

It’s an absolute pleasure. And if there are ever any questions, please feel free to reach out. For patients who reach out, we are there to talk to all of you and give advice as good as we can or put you in contact with the right people.   

Katherine Banwell:

Thank you. And thank you to all of our collaborators. To learn more about AML and to access tools to help you become a proactive patient, visit powerful patients.org. I’m Katherine Banwell. Thanks for joining us today.