AML treatment Archives - Page 3 of 9

How Does the Presence of Molecular Markers Affect AML Care?

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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.

Advocacy Tips From an AML Patient

March 13, 2023/in Acute Myeloid Leukemia, AML Activated, AML Activated Activity Guides, AML Newly Diagnosed, AML Programs, AML Treatments and Clinical Trials, AML Video ND, AML Video TC /by Kara Rayburn

Advocacy Tips from an AML Patient from Patient Empowerment Network on Vimeo.

AML patient and Empowerment Lead, Sasha Tanori, shares her advocacy tips, and the importance of being honest and open with your oncologist.

How Does One’s Culture Impact AML Care

Related Resources:

What I Wish I Knew Before My AML Diagnosis

How I Overcame Biases During AML Treatment

Transcript:

Sasha Tanori:

Okay, so my number one thing, I guess I could…a tip sort of that I can give to women specifically or non-gendered people, if you want kids, I would definitely say to talk to your doctor as soon as you find out, even before you start doing the chemo, if you can just really, really talk to them and see, I think there’s anything that they can do for preserving your eggs for the future, because even though it may seem like you know it’s just no, not big deal. Not everyone gets the opportunity again. I know there are some people out there who might be able to, but it’s not a guarantee. And it sucks to have that opportunity kind of taken from you in a way, and I know it’s not something that you’re thinking like, “Oh well, it’s life for death.” And…yeah, I understand, and I get that, but in the moment, it may feel that way, but you never know how are you going to feel five, six years down the line when you’re pushing 30 and you’re like, “Oh my gosh, My opportunity is gone. You know, there’s nothing I can do about it.”

So that would be my number one tip. Definitely to be honest. Be honest and open with your oncologist, find some type of tips or tricks, or even if you just need someone to talk to about the infertility…it’s definitely worth it. Another thing I would say is to be really, really open with your oncologist about everything you’re going through. Nothing is too embarrassing and I know that’s a lot easier said than done, but I think being honest about what you’re going through, whether it’s mentally, if you’re going through depression, anxiety, if you’re having suicidal thoughts or tendencies, that’s definitely something you should talk to your oncologist about, so they can help you reach out to find some type of counseling. Mental health is very, very important when it comes to this. Your mental health will make or break you during this journey, and you have to find some type of close community, whether it’s your friends, your friends, your family, or just your oncology team, like someone that you could reach out to and talk to about everything, lay it all on the table and now I’m feeling guilty because I survived that my friend didn’t, or I’m feeling anxious because I have the scan coming up, and this is the third one in like two months, you know? There’s so much things that are going on in your head and to keep it to yourself, it’s a lot and it’s not fair to you, you need to be able to speak up and tell people what you’re going through, it doesn’t matter who it is if it’s your friend, your mom, even your oncologist, but they’re going to understand and they’re going to help you.

There are lots of resources out there that will definitely make this a lot easier. Another tip I would say is, talk to your oncologist about the good, the bad, and the ugly when it comes to your side effects because if you stay quiet about it, you’re going to really regret it. There have been many times where I was just too embarrassed to be like, :Oh you know what, I have this really bad rash on my butt, and I don’t know what to do about it.” So finally, they’re like, “Why didn’t you say something? Oh yeah, we can give you a cream, or we can do this or that for you.” And you’re just like, “Oh, okay, that feels so much better. Thank you.” But at the time, you’re probably just like, “Oh my God, I’m so embarrassed, I don’t want anybody to know about this. I don’t even want to tell my parents, I don’t want to tell my friends.” But I mean, this is all related to your cancer journey, one bad side effect can lead to something else, which could lead to something else. So it’s very, very good to try and be open and honest when it comes to your side effects, your emotions, your body, if you’re gaining weight or losing weight, if you’re losing your hair again, if you’re losing your eyebrows, you know talk to them, find out if there’s any solutions that can help because…

It’ll definitely make a big difference. I would say definitely another big thing would be to try and build a community through social media. Having friends or even just strangers on your feed that you see go through the same things you go through makes you feel so much less alone. I have been able to… I’m very happy that I’ve been able to make friends on social media through Instagram, Facebook, Twitter, just start adding everybody goes on Facebook groups that are specifically for AML, so you can just type in AML recovery, AMLl survivors, AML, family groups, caregivers. There’s a lot of things out there that are definitely beneficial and it helps to talk to others about it, so you feel less alone. Definitely. So I think those would be my biggest tips for expressing your advocacy.

Share Your Feedback About [ACT]IVATED AML

How I Overcame Biases During AML Treatment

March 13, 2023/in Acute Myeloid Leukemia, AML Activated, AML Activated Activity Guides, AML Newly Diagnosed, AML Programs, AML Treatments and Clinical Trials, AML Video ND, AML Video TC /by Kara Rayburn

How I Overcame Biases During AML Treatment from Patient Empowerment Network on Vimeo.

AML patient and Empowerment Lead, Sasha Tanori, shares how she had to overcome several biases to get doctors to take her symptoms seriously.

How Does One’s Culture Impact AML Care

Related Resources:

What I Wish I Knew Before My AML Diagnosis

Advocacy Tips From an AML Patient

Transcript:

Sasha Tanori:

So, of course, I can’t speak for everybody, but of course for me, I am Mexican American, I’m from a little small area called The Imperial Valley, it’s like at the very, very bottom of California, and it’s literally like 20 minutes away from Mexico. So right off the bat, I experienced a lot of low-income poverty type of bias, I guess you could say. And then being plus size, that was another thing when I initially first went…I remember one of the first things that they told me, I was like, “Well, first of all, you’re obese, and you need to lose weight.” And I was like, “Well, I have to deal with the bruises?” And they were like, “Well, maybe your body.” They’re just coming up with different excuses as to why, maybe it’s because I have this problem or that problem, and I was just like, “Well, no, I don’t really think that’s the issue.” So then they had misdiagnosed me, I got sent home and then when I had went back to the hospital, that was another thing they brought up again, I was in the hospital, because I had a giant bruise on my lower back, and it was like I looked like a tire mark. And they were like, “Okay, well, it says here that your BMI is high.” And I’m like, “But what…what does me being plus-sized have to do with the giant bruise on my back? This doesn’t make any sense.” No correlation, nothing.

So that was another big thing that just has always irritated me my entire life, I’ve always been a pretty big chubby girl, so if I had hurt myself they would always bring up my weight somehow it’s just like, that is looking to do with me breaking a bone or me having the cold or something dumb like that. So that was another thing that kind of bugged me whenever I was first diagnosed, they would always kind of bring up your weight, and another thing is that because I live in a low-income community, we don’t have resources like cancer doctors down here, I think there’s like maybe two and they’re not even in my local town, they’re in the town over. That’s like a 10-minute drive. So when I was first diagnosed, I was at the hospital for 12 hours. I was there with my mom and they had no clue what was wrong with me, so then I got sent to San Diego, which is like two-and-a-half hours away, and when as soon as I got there, within like 30 minutes, I was diagnosed with cancer.

So that’s how quickly they were able to catch it and everything, but in my local town they had no clue what was wrong, they didn’t know it was cancer, they didn’t know what was going on. They just kept doing tests after tests after tests, and they’re on blood work, and finally, they were just like, “We have no clue, we’ve got to send you somewhere else. You’ve got to get in an ambulance and leave.” So we were just like, “Okay.” So yeah, that was definitely something that…it has a lot to do with my culture. I live in a small mostly Mexican-driven city location, I guess the Imperial Valley is like a valley, I guess it has five or six different little towns all put together, so a majority of us are Mexican, so we’re considered low-income poverty, we don’t have a lot compared to when it comes to bigger towns like LA or San Diego or San Francisco, but yeah, I think those were my biggest issues. And then, of course, being a woman. No matter what, you’re always going to get that. People aren’t going to take you serious. We’re going to get that, “Oh, man, she’s just overreacting. She’s on her period,” or your typical misogynist stuff that people say about you. But those are my biggest things or I guess adversities that I had to go through when it came to my cancer journey.

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What I Wish I Knew Before My AML Diagnosis

March 13, 2023/in Acute Myeloid Leukemia, AML Activated, AML Activated Activity Guides, AML Newly Diagnosed, AML Programs, AML Treatments and Clinical Trials, AML Video ND, AML Video TC /by Kara Rayburn

What I Wish I Knew Before My AML Diagnosis from Patient Empowerment Network on Vimeo.

AML patient and Empowerment Lead, Sasha Tanori, shares what she wishes she knew and what to ask before her AML diagnosis, and the importance of advocacy.

How Does One’s Culture Impact AML Care

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Transcript:

Sasha Tanori:

So, one of the biggest things I wish I knew, especially before, was the whole saving your eggs type thing for fertility. That’s one of the biggest things that I honestly really regret because here it is almost what…five, six years later, and I, unfortunately, am infertile, so it really does suck because that was something that I was really looking forward to in my life was like being a parent or being a mom, and at the time, it’s just like…everything happened so fast, it was like, Okay, we’re going to…We did the chemo, and now we’re going to do a couple more rounds and then it’s like, Oh, we found a donor, so you could have your bone marrow transplant…oh my gosh, I can’t say the word, your bone marrow transplant. I think I had mentioned it to my doctor, but he was like, “Well, if we wait, now we’re going to lose the person who’s going to donate to you.” And I was like, “Okay, well, we need to hurry up and get that done, get it over with.

So back then, I really wish I would have advocated for myself more, ask more questions and because thinking back, I’m like, I don’t mind if I would have waited until after having my eggs frozen to find another donor, I think that possibly there could have been someone else out there.

But I think it was just in such of that state of mind of like, “I need to hurry and get this done. It’s life or death, I’m going to possibly die type of situation.” But you know I’m like, “No, I think I would have been okay if I would have waited another month or so until after I froze the eggs.” But you live and you learn, and there’s not really much you can do about it now, unfortunately. But at the time, I really wish that I would have spoken up and advocated for myself more if I would have known that that was going to happen, because like I said, five years later infertile can’t really do anything about it, you know? Yeah, my life is saved, but I can’t have kids though, so you just kind of think it heartedly about it, but yeah, that’s one of the things I really wish I would have advocated for myself more about. For now, I think everything else has been kind of…it’s been good. I mean, I’ve taken it step by step, by day, you just got to put on your big girl panties or put on your big girl shorts, I guess you could say, and just continue going about your day, you gotta wake up, do your job, take care of your family, take care of your life.

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How Does One’s Culture Impact AML Care?

March 13, 2023/in Acute Myeloid Leukemia, AML Activated, AML Activated Activity Guides, AML Newly Diagnosed, AML Programs, AML Treatments and Clinical Trials, AML Video ND, AML Video TC /by Kara Rayburn

How Does One’s Culture Impact AML Care? from Patient Empowerment Network on Vimeo.

AML patient and Empowerment Lead, Sasha Tanori, shares how her culture impacted her care and how her diagnosis opened her family’s eyes to start taking care of themselves.

What I Wish I Knew Before My AML Diagnosis

Related Resources:

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Transcript:

Sasha Tanori:

My culture made a big significance in my care, because it was something that my family, especially my dad with the Mexican side, it wasn’t something that you did. You didn’t go out and seek care if you are hurt, you just sucked it up, you went to work, you went to school, you did your job, you took care of your family, and that was it. If you had any type of ailments or illness, you would just rub some Vaseline and do the sana sana and just move on about your day. So when I started getting the bruises and the tiredness and the fatigue, my dad was just like, “She’s just clumsy, she’s just making it up, or she’s being dramatic,” and it was never a big deal to anybody, especially with him. You know my mom, she’s a little bit more on my side with everything, so she was like, “Oh yeah, you know, maybe you should go to the hospital. Maybe you should go check this out, maybe you should go do that.”

But finally, it was my cousin who convinced me about like a month after all, I was going through all of that to go to the hospital, and still my dad was just like, “Man, she’s going to go to the hospital and be there for 12 hours, and nothing’s going to be wrong.” He was so sure that everything was fine, so finally, when I had went, and I found out I had cancer, I think it really opened my dad’s eyes to realize, “Wow, maybe she wasn’t lying.”

Maybe she wasn’t making it up. But yeah, I think it was a really big step on my part being Mexican American, to finally take that step to take care of myself, especially physically and mentally, you know? God forbid, you have depression or anxiety in a Mexican household, they’re just like, “No, no, no, there’s no…what do you mean you don’t feel good? Just walk outside, drink some coffee, you’ll be fine. Get over it.” So yeah, I think it really opened my dad’s eyes, especially seeing me so sick for him to kind of realize, “Wow, you know, this stuff is kind of serious.” Because now he goes to the doctor, he takes his medication, he takes care of himself more.

But yeah, having that type of cultural background in your household, it’s really hard to express how you’re feeling when it comes to your mental and physical health. It’s hard to walk up to your dad and be like, “Hey, Dad, I’m not feeling good, can you take me to the doctor? Or can we talk about this?” And she’s like, “No, no, no. We don’t talk about stuff. No, we don’t go to the doctor, we don’t do any of that stuff, we have to stay strong and work and take care of the family.” We’re not allowed to be sick, we’re not allowed to take care of ourselves pretty much, I think…

Thankfully, me taking care of myself has kind of helped him as well to take care of himself.

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[ACT]IVATED AML Resource Guide en español

March 1, 2023/in Acute Myeloid Leukemia, AML Activated, AML Activated Resource Guides, AML Newly Diagnosed, AML Programs, AML Resource ND /by Kara Rayburn

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What AML Mutations Are Associated With Adverse Outcomes?

February 1, 2023/in Acute Myeloid Leukemia, AML Activated, AML Activated Experts, AML Newly Diagnosed, AML Programs, AML Treatments and Clinical Trials, AML Video ND, AML Video TC /by Kara Rayburn

What AML Mutations Are Associated With Adverse Outcomes? from Patient Empowerment Network on Vimeo.

Which acute myeloid leukemia (AML) mutations are linked to adverse outcomes? Dr. Naval Daver from the University of Texas MD Anderson Cancer Center shares insight..Learn about different mutations, treatment options, and the importance of testing.

[ACT]IVATION TIP from Dr. Daver: “Check for mutations to the frontline setting…absolutely, these include FLT3, IDH1, IDH2, TP53, and NPM1 MLL this list will likely continue to grow as we get more targeted therapies in immunotherapies and find benefit in particular subsets, but also in the relapse setting to not depend on the baseline molecular profile because the lipids actually can change. We do see AML as a multiclonal disease, and there can be emergence and escape of different clones, so to check again in the relapse for those same mutations and both in the frontline, the relapse setting.“

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Transcript:

Art:

Dr. Daver, what mutations are associated with adverse outcomes in AML? What are the best time points to check for these mutations, and what therapeutic options do you consider for patients or harboring these mutations?

Dr. Naval Daver:

This is very, very important, a mutational targeted therapy is probably the biggest overarching change that has occurred in acute myeloid leukemia in the last decade, and of course to implement those therapies. One has to know the mutational profile, the five big mutations that whenever I speak to my patients in clinic today that I talk about wanting to know before I embark on any therapy are FLT3 or FLD3, IDH1, IDH2, TP53, and now, more and more recently, NPM1 or MLL, actually six different mutations, cytogenetic operations, and the reason is that we do have targeted therapies for these mutations, some of these targeted therapies are already approved in the frontline setting like the FLT3 inhibitors, some of these are being evaluated in ongoing Phase III studies like the CD47 magrolimab for TP53.

As well as the menin inhibitors now in frontline setting in combinations of intensive chemo or HMA venetoclax (Venclexta), or MLL NPM1 but I think identifying these targets and getting the patients on the right clinical trial personalized to that target for them has historically shown significant improvements, 20 to 30 percent survival improvements in FLT3, IDH and potentially for the TP53 MLL NPM-1 so definitely on newly diagnosed, I would recommend getting that information and then going on to either standard of care the drugs already approved or clinical trial that incororates that targeted therapy or immunotherapy for a target in the relapse setting the two most important mutations today, or the three most important are FLT3, then IDH as well as MLL NPM1.

Three inhibitors like gilteritinib (Xospata) are already approved. Similarly, IDH inhibitors and combinations of gilteritinib or IDH with venetoclax are really showing very good outcomes, even in relapse three, which about 20 years ago was a very, very, very poor outcome. T

oday, we can get up to 80 percent of these patients to remission, half of them into transplant, and a good number may have long-term survival post-transplant, so it’s very important to not mislead to an IDH1, IDH2 to a relapse setting.

And then now with the menin inhibitors we’re also looking in all our patients for MLL rearrangement, NPM1 in relapse, because this could open the door for menin inhibitor-based therapy, which again can give up to 50 percent remission and a path to transplant. Now many patients at MD Anderson who have gone through too many inhibitors, transplant and are alive and ongoing at two and three years.

So the bottom line is, it’s important you check at my activation tip for this question is it’s important to check for mutations to the frontline setting…absolutely, these include FLT3, IDH1, IDH2, TP53, and NPM1 MLL this list will likely continue to grow as we get more targeted therapies in immunotherapies and find benefit in particular subsets, but also in the relapse setting to not depend on the baseline molecular profile because the lipids actually can change.

We do see AML as a multiclonal disease, and there can be emergence and escape of different clones, so to check again in the relapse for those same mutations and both in the frontline, the relapse setting.

To try to get on to a therapy, whether it’s approved or clinical trial that incorporates those targeted therapies, which has historically shown a significant improvement in both response and long-term survival.

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BIPOC Patients Living With AML | Mortality Rate and Favorable Genetics

February 1, 2023/in Acute Myeloid Leukemia, AML Activated, AML Activated Experts, AML Newly Diagnosed, AML Programs, AML Treatments and Clinical Trials, AML Video ND, AML Video TC /by Kara Rayburn

BIPOC Patients Living With AML | Mortality Rate and Favorable Genetics from Patient Empowerment Network on Vimeo.

How can acute myeloid leukemia (AML) disparities be addressed in BIPOC groups? Dr. Naval Daver from the University of Texas MD Anderson Cancer Center shares insight. Learn about disparities, molecular profile cytogenetics, and clinical trial benefits.

[ACT]IVATION TIP from Dr. Daver: “Clinical trials are usually developed to improve and move forward the standard of care to better outcomes, as well as knowing that there are many different approaches to getting financial support through different organizations, entities and even potentially through some of the clinical trials, as well as considering becoming volunteer donors for national marrow donor programs, so you can support potential transplant for patients from those communities, which will give them a potential curative option.”

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Transcript:

Art:

Dr. Daver, non-Hispanic Black and Hispanic patients with AML have higher mortality rates than non-Hispanic white patients despite more favorable genetics and younger age. How can we address disparities in AML among diverse patient populations?

Dr. Naval Daver:

This is a great question, and then something that I think we all need to spend more time with understanding, and now researchers started to look at the differences in molecular profile cytogenetics presentations among different ethnic backgrounds. It is definitely true that access to care has been more limited in some of these populations that you mentioned, including the Hispanic population and in the non-Hispanic Black population, and I think there are a number of things that may be causing this issue, so I think one there is definitely an economic divide, and especially for large academic centers where patients do have to travel, often stay locally for a period of time to go on the trial, this causes expense, and a lot of times,I think a number of these populations may not have had funding or they may not have the insurance that would cover that particular center.

And so this is one of the big hurdles… second, I think that there is among us communities, sometimes more suspicion or circumspect approach to clinical trials and large academic centers thing, that’s something that hopefully we will be able to change with programs such as the and many, many others that we all are working on, because I think we actually do want to have more inclusion in clinical trials. And we do want to have a more representation of the entire population rather than just a subset.

So hopefully the understanding that clinical trials are usually done with the intent to improve the current standard of care, and randomization includes the current standard of care, and then something that we think could be added to further improve that, and often that many of the clinical trials may even be able to provide some degree of financial support for travel stay.

These could all help maybe some of these populations to access and get on clinical trials, which is one of the big goals for MD Anderson and other large academic centers and investigators such as myself.

I think the third big hurdle, of course, is that even proven extensive transplant, which still remains the most effective long-term curative approach, we don’t have as many donors for the Black and the Hispanic community proportionately than we do for the Caucasian white population.

So I think this is another kind of call to voluntarily consider becoming a donor for the national marrow donor program, for others who are in that community, because we often do find challenges finding ideal donors, and this is a very simple procedure where it…here one, all you have to do is give us a saliva swab, mail it in.. You don’t even have to go to the clinics.

Nowadays, they log it in and if you’re ever called on, it’s just a blood collection, it’s like donating in blood, and you could save somebody’s life to be probably the easiest thing to save, somebody’s like that you will have the opportunity to do in your life.

So I think it’s really, really important that those communities also start signing up and becoming voluntary donors, so I think these are three of the kind of hurdles, of course, there are many, many others, but hopefully with the big push and impetus that’s happening across the world and across the country and across the large academic centers. In the next five to 10 years, we will see more inclusiveness and more representation of all populations proportionally in the ongoing trials and publications.

My activation tip for this is understanding that clinical trials are usually developed to improve and move forward the standard of care to better outcomes, as well as knowing that there are many different approaches to getting financial support through different organizations, entities and even potentially through some of the clinical trials, as well as considering becoming volunteer donors for national marrow donor programs, so you can support potential transplant for patients from those communities, which will give them a potential curative option.

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Challenges in Treating TP53-Mutated AML, Hope on the Horizon

February 1, 2023/in Acute Myeloid Leukemia, AML Activated, AML Activated Experts, AML Newly Diagnosed, AML Programs, AML Treatments and Clinical Trials, AML Video ND, AML Video TC /by Kara Rayburn

Challenges in Treating TP53-Mutated AML, Hope on the Horizon from Patient Empowerment Network on Vimeo.

TP53-mutated acute myeloid leukemia (AML) treatment has some challenges. Dr. Naval Daver from the University of Texas MD Anderson Cancer Center shares his perspective. Learn about promising treatments on the horizon for this AML subgroup.

[ACT]IVATION TIP from Dr. Daver: “The TP53 mutation remains the most difficult subset of acute myeloid leukemia, there is hope on the horizon with new treatments such as CD47 antibodies and targeted therapies like APR that are being looked at, and also a strong consideration for allogeneic transplant in TP53, because this seems to be the only modality associated with a good chance of cure after achieving remission with one of the frontline therapies.”

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Transcript:

Art:

Dr. Daver, what have we learned about TP53-mutated AML? And what is the takeaway for these patients?

Dr. Naval Daver:

TP53-mutated AML remains the most difficult molecular subset of all acute myeloid leukemia. Patients who have this mutation, unfortunately, do not respond well to any of the established standard care therapies, including intensive chemotherapy, the HMA alone, such as azacitidine (Onureg or Vidaza), decitabine (Dacogen) alone, or even HMA venetoclax (Venclexta) with all of these, we do see responses, especially with HMA venetoclax or intensive chemotherapy, we can see 15 to 55 percent remission rate, but the remission, very short lived, early relapses and the median overall survival across all of these currently available standards of cares are between six to 10 months.

So there has been an intense effort in the last six, seven years to develop TP53-directed therapies or therapies that will work regardless of TP53 mutation, and there are two drugs this time that are very promising and being evaluated as ongoing Phase II and Phase III studies.

One of them is an immunotherapy drug called magrolimab which seems to have very similar activity and probability with good response rates in TP53-mutated AML. This has been completed in a single arm phase 1B study in front line TP53-mutated AML where we saw close to 50 percent CR, CRI complete permission rates. And median survival was above 11 months in older unfit TP53, which is better than any survival we have seen in the past in this population.

The other study was with the oral care targeted therapy towards TP53, called APR, and this therapy was specifically designed to target the TP53 mutation, and this is being evaluated in the frontline setting in combination with a society in venetoclax. We hope that these regimens are these novel therapies, one or both of them will be able to at least incrementally improve their current outcomes in TP53.

The other area where we have really been doing a lot of research, and I think the data is suggesting, is that allogeneic transplant may work for separate, and we are routinely considering transplant in these patients in the frontline setting, once they are able to achieve remission.

My activation tip is the TP53 mutation remains the most difficult subset of acute myeloid leukemia, there is hope on the horizon with new treatments such as CD47 antibodies and targeted therapies like APR that are being looked at, and also a strong consideration for allogeneic transplant in TP53, because this seems to be the only modality associated with a good chance of cure after achieving remission with one of the frontline therapies.

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A Look at Ongoing Acute Myeloid Leukemia Phase III Trials

February 1, 2023/in Acute Myeloid Leukemia, AML Activated, AML Activated Experts, AML Newly Diagnosed, AML Programs, AML Treatments and Clinical Trials, AML Video ND, AML Video TC /by Kara Rayburn

A Look at Ongoing Acute Myeloid Leukemia Phase III Trials from Patient Empowerment Network on Vimeo.

What are the acute myeloid leukemia (AML) Phase III clinical trials that are ongoing? Dr. Naval Daver from the University of Texas MD Anderson Cancer Center shares his perspective about encouraging trials. Learn about the MORPHO Study and others.

[ACT]IVATION TIP from Dr. Daver: “The maintenance with gilteritinib and the MORPHO Study, as well as the relapsed refractory study as well as the use of a e-selectin inhibitor called uproleselan, and hopefully this will lead to approval of the next batch of three or four drugs, which will further improve outcomes for frontline as well as relapsed AML.”

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Transcript:

Art:

Dr. Daver, can you speak to some of the ongoing Phase III trials in AML, what are you most excited about?

Dr. Naval Daver:

This time there are numerous ongoing phase three in acute myeloid leukemia, some in the frontline, some in the relapse setting. In the frontline setting, the ones that I’m most excited about are trials incorporating a novel immunotherapeutic pathway called the CD47 antibody that works to activation of macrophages, these are looking at a very high-risk molecular group of acute myeloid leukemia, the TP53 in adverse cytogenetics, and there are two randomized phase threes with this agent, one focused on TP53 mutated AML looking at the azacitidine and magrolimab versus the current standard of care FDA-approved azacitidine-venetoclax (Onureg or Vidaza-Venclexta) in TP53 mutated.

The other is actually looking at all older unfit AML so trying to improve on azacitidine venetoclax doublet with a triplet, so this is looking at azacitidine venetoclax magrolimab versus azacitidine-venetoclax placebo so if both of these trials are positive, then this will lead to incorporation of immunotherapy in the frontline setting in AML, which is exciting and something we’ve been working towards for the last 10, 15 years.

The other Phase III trials in the frontline setting or in the maintenance setting really that I’m excited about is called the MORPHO Study…this is using a FLT3 inhibitor gilteritinib (Xospata) as a maintenance post-transplant, so we know FLT3-mutated patients respond well, when they receive intensive induction FLT3 inhibitor, we still need to take them to transplant because even though the initial response is good, many can relapse.

So we actually try to give to the cycles of intensive induction for the move to transplant, and then if we start there, we still see at about 40 percent of these patients can relapse in the next three years, so this has led to efforts to add a maintenance FLT3 inhibitor gilteritinib single agent post-transplant as a maintenance for one to two years versus placebo observation, which has historically been a standard of care, and so this is being looked at a large multi-center called the MORPHO Study that we hope to get data from in the near future.

Another study in the similar design that’s being done by the UK cooperative group is looking at maintenance with the oral azacitidine, post-transplant for non-FLT3, so similarly, can we overall improved outcomes not just for FLT3, but the general patient population is going to transplant by using the maintenance oral azacitidine post-transplant versus placebo.

And in the relapse setting, there is a very novel unique oral therapy drug called uproleselan, which is an e-selectin inhibitor, and this agent is now being combined with traditional salvaged chemotherapy such as FLAG-Ida mec versus the placebo mec plus FLAG-Ida or mec in the relapse setting.

And that’s what he’s actually been completed to enrollment, and we’re hoping to hear data from that in the near future. So these are the major randomized studies focusing on TP53, FLT3, and relapsed refractory AML that we’re looking for in the near future and hopefully could lead to two or three more new approvals in the AML space.

My activation tip for this question is that there are ongoing numerous frontline Phase III as well as relapsed refractory Phase III, targeted immunotherapy approaches, specifically among these we’re excited about the CD47 antibodies. The maintenance with gilteritinib and the MORPHO Study, as well as the relapsed refractory study as well as the use of a e-selectin inhibitor called uproleselan, and hopefully this will lead to approval of the next batch of three or four drugs, which will further improve outcomes for frontline as well as relapsed AML.

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What Does Triplet Therapy in AML Mean for the Future?

February 1, 2023/in Acute Myeloid Leukemia, AML Activated, AML Activated Experts, AML Newly Diagnosed, AML Programs, AML Treatments and Clinical Trials, AML Video ND, AML Video TC /by Kara Rayburn

What Does Triplet Therapy in AML Mean for the Future? from Patient Empowerment Network on Vimeo.

What do acute myeloid leukemia (AML) patients need to know about triplet therapy? Dr. Naval Daver from the University of Texas MD Anderson Cancer Center shares his perspective. Learn about the meaning, progress, and outlook for triplet therapy.

[ACT]IVATION TIP from Dr. Daver: “Some of the early data with the FLT3 inhibitor as well as the CD47 antibody triplets are showing very, very promising activity and are now moving into larger multi-center and randomized studies.”

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Transcript:

Art:

Dr. Daver, what does triplet therapy in AML mean for the future?

Dr. Naval Daver:

So when we say triplet therapy, what we’re really thinking about is building on the existing FDA-approved combination of HMA venetoclax (Venclexta), so as a background venetoclax, showed a CR, CRI which is a complete remission rate of about 70 to 75 percent with the median survival in 15 months.

This was in older patients, about 75 years in age, those who were not considered fit for intensive chemotherapy, although this was a major step forward in comparison to what we have seen with traditional low intensities with azacitidine (Onureg or Vidaza), decitabine (Dacogen) alone, we do see the three-year survival is about 25 to 30 percent.

So this is progress compared to 10 percent long-term survival, we used to get a decade ago, but, of course, we want to improve on that. Also, a molecular analysis of data has shown that there are certain molecular subsets that don’t respond as well to azacitidine, venetoclax or if they respond they relapse quickly these include FLT3 mutated and the TP53 mutated as well as potentially MLL rearranged.

And so here we have started incorporating the targeted therapies like inhibitors like the menin inhibitors like CD47 antibodies to target those specific high-risk or bad molecular cytogenetic groups, and we are seeing that with the combinations of these three drugs, especially for those particular molecular subsets.

So azacitidine and venetoclax for FLT3 inhibitor for FLT3 mutator, azacitidine, and venetoclax, magrolimab for TP53 mutated, the response rates that we’re getting, as well as the depth of response and the early trends towards survival are looking very, very promising compared to what we have seen with azacitidine venetoclax alone.

So we believe, and I personally believe that these three drug combinations, the so-called triplets will actually be eventually the way to go forward now, that means that one has to realize that when you add a third drug, there is a cumulative myelosuppression, azacitidine-venetoclax is already a myelosuppressive regimen.

Yes, it’s manageable, but it is myelosuppressive. And the third drug, this can become more cumulative, so we have been working for the last three, four years and continue to work on those optimization because since we are seeing true synergy but pre-clinically and what we think in the clinic, we are not needing to give full doses and we’re doing reduced durations of venetoclax and those with FLT3 inhibitor, and now we feel that some of those triplets are actually giving very, very, very good efficacy.

There’s a lot of discussion in the community of whether we need to combine all two drugs up front or can be sequence these drugs or can we introduce a targeted therapy based on a molecular escape, and I think a lot of these will have to be evaluated and many of these are being looked at in various trials, but I do think the bottom line is that bringing in your targeted therapy or immunotherapies early on in the frontline setting and some way or the other is probably where you’re going to get the most bang for the buck and the most benefit in curing patients long-term rather than trying to reserve them for the salvage, because in salvage AML historically, nothing has really been able to improve the long-term cure rate significantly.

So the activation tip for this question is that now with the identification of certain molecular subsets that have poorer outcomes with the HMA venetoclax, we have started incorporating targeted and immunotherapies in the earlier settings, either up front in the three drug combination or an early sequential approach.

And we believe that with such combinations, we may be able to achieve deeper remission and longer responses. Some of the early data with the FLT3 inhibitor as well as the CD47 antibody triplets are showing very, very promising activity and are now moving into larger multi-center and randomized studies.

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A Look at Lower Intensity Chemotherapy in Untreated AML

February 1, 2023/in Acute Myeloid Leukemia, AML Activated, AML Activated Experts, AML Newly Diagnosed, AML Programs, AML Treatments and Clinical Trials, AML Video ND, AML Video TC /by Kara Rayburn

A Look at Lower Intensity Chemotherapy in Untreated AML from Patient Empowerment Network on Vimeo.

Dr. Naval Daver from the University of Texas MD Anderson Cancer Center discusses whether untreated acute myeloid leukemia (AML) can be treated with lower intensity chemotherapy.

[ACT]IVATION TIP from Dr. Daver: “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. Daver, what are we learning about patients with untreated AML who are ineligible for intensive chemotherapy? Will intensive chemotherapy, a thing of the past, in the near future?

Dr. Naval Daver:

There has been a major shift over the last four or five years towards using lower intensity combinations, such as azacitidine (Onureg or Vidaza) and venetoclax (Venclexta) and patients who are definitely about 75 and not fit for intensive induction. I don’t think anybody debates in that population, but even in patients 60 to 75 years away, you are borderline, and maybe we could give intensive induction chemotherapy and get patients to through it with support of care, antifungals, antibiotics by close monitoring, but we’re seeing similar remission rates with azacitidine (Vidaza), venetoclax (Venclexta), much less toxicity, less mortality, and especially the goal is to get a number of these patients to allogeneic stem cell transplant, which it is.

Then we feel that the lower intensity, better tolerated, smoother remission getting patients in a good condition an allogeneic transplant may be the way to go now, of course, to really make the standard of care, we have to look at this in a randomized fashion to make sure that what we believe is actually what the data is going to confirm, so there is an ongoing randomized study looking at the azacitidine and venetoclax intensity versus the traditional intensive chemotherapy called three plus seven in patients 18 to 65 years of age, and that…then you will, I think, give us a lot of information and data as for whether we can start for placing intensive chemotherapy for a large proportion or majority of AML patients, even those who are younger.

Today, I don’t think that in terms of chemotherapies are a thing of the past, I think those patients who are below 60 or even those who are 60 to 65, who are routinely doing intensive induction chemotherapy, one has to realize that the five-year survival for many molecular subsets are close to 50 to 60 percent with intensive induction chemotherapy, whereas with HMA venetoclax in the older unit, we’re looking at three to five-year survival rates of about 30 percent, so we have still not seen data and younger patients with Hamas to be convinced that this will replace intensive chemotherapy altogether, I think the signal suggests that there is a potential for it to do so, especially with the use of allergenic tensor as plan, which we’re using quite frequently and…or maintenance.

But that has not yet been established. So I would still say we do use intensive chemo in those who are young and fit, so my activation tip for this is that there has been a lot of progress in the lower intensity therapies over the last six or seven years.

A decade ago would not even be asking whether there’s anything that can replace intensive chemo today we do have data with HMA venetoclax that suggest that it may be as good as intensive chemo looking at the response rates MRD negativity, and especially with three drug combinations where adding targeted therapies to HMA venetoclax, those response rates and depth of response looking as good, if not better, than intensive chemo there are randomized studies ongoing that are going to be looking at intensive chemotherapy versus HMA venetoclax and if those show equivalents or superiority for HMA venetoclax, I think in the next five, six years there will be a huge shift towards less use of intense and chemotherapy in the frontline setting, but we’re not there yet.

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AML Clinical Trials Critical to Treatment Breakthroughs and Improvements

February 1, 2023/in Acute Myeloid Leukemia, AML Activated, AML Activated Experts, AML Newly Diagnosed, AML Programs, AML Treatments and Clinical Trials, AML Video ND, AML Video TC /by Kara Rayburn

AML Clinical Trials Critical to Treatment Breakthroughs and Improvements from Patient Empowerment Network on Vimeo.

Why are acute myeloid leukemia (AML) clinical trials so critical? Dr. Naval Daver from the University of Texas MD Anderson Cancer Center shares his perspective about clinical trials. Learn how clinical trials help both current and future AML patients.

[ACT]IVATION TIP from Dr. Daver: “Clinical trials are critical, both for the patients themselves to get access to what we call tomorrow’s medicine today as well as potentially to help move the entire field forward.”