Black and Latinx AML Patients | The Impact of Cultural Beliefs

Black and Latinx AML Patients | The Impact of Cultural Beliefs from Patient Empowerment Network on Vimeo.

What impact can cultural beliefs have for Black, Latinx, and other AML patients? Expert Dr. Sara Taveras Alam from UTHealth Houston explains how experiences, cultural beliefs, and religious beliefs can impact AML care and patient advice to help inform your care provider about your viewpoint.

[ACT]IVATION Tip

“…voice your beliefs, so that your providers are aware of your goals and the barriers to care possibly and inform you better on how we can accommodate for your beliefs and improve upon the expectation that you may have from the healthcare system from previous experiences.”

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Transcript: 

Lisa Hatfield:

Dr. Taveras, what impact do cultural beliefs and practices surrounding illness and treatment-seeking behaviors have on delays in AML diagnosis and disparities and treatment adherence within the Black and Latinx communities?

Dr. Sara Taveras Alam:

Thanks for this question. The experience that the patients may have had previously with the medical system, or that their family members or friends may have had previously with the medical system may impact their initial care. It may be initially that patients, of course, don’t know that this is what’s going on, and they think that they have some flu or viral infection, or does not know the severity of the situation, and especially if the personal or family experience with health care has not been positive, this may cause delays in presenting to tuition and obtaining a diagnosis. Unfortunately, we know that Black patients tend to be diagnosed with AML at an earlier age, and we know that they might not respond to treatment as well as their non-Hispanic white counterparts.

So it’s important to know this because young patients may not really foresee that they may be ill in this way and not seek care promptly. So with AML, the time to care is not necessarily going to cost progression of disease, but the patient may have complications from their disease by the time that we make the diagnosis and that can make things a little bit more challenging. Unfortunately also, Black and Latin communities can face higher complication rates from treatment, and that is something that we have seen in several clinical trials.

In the specific situation of Latin communities and well not only Latin communities, but other patients with strong religious beliefs and for Jehovah’s Witnesses specifically, this is a very challenging disease because patients who are Jehovah’s Witnesses do not accept transfusions and unfortunately we know that if the patients with acute myeloid leukemia are unable to be treated appropriately without transfusion. They may need transfusions because of their illness, and we know that with chemotherapy, unfortunately, the hemoglobin could get worse before they get better.

So it’s almost a guarantee that even if a patient with AML does not need a diagnosis, does not need a transfusion at presentation, it’s almost guaranteed that they will need a transfusion at some point during the course of their treatment. So this makes it very challenging for patients who have that religious belief and may require involving their religious leader and can cause a lot of conflict within their family members, unfortunately.

My activation tip for this question is to voice your beliefs, so that your providers are aware of your goals and the barriers to care possibly and inform you better on how we can accommodate for your beliefs and improve upon the expectation that you may have from the healthcare system from previous experiences.

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How Can Bone Marrow Biopsies Be Used in AML Care?

How Can Bone Marrow Biopsies Be Used in AML Care? from Patient Empowerment Network on Vimeo.

How do AML care providers use bone marrow biopsies in patient care? Expert Dr. Sara Taveras Alam from UTHealth Houston explains how the tests are used and shares patient advice for lifestyle and dietary precautions against infections.

[ACT]IVATION Tip

“…in terms of going out in the world, I would avoid for our AML patients to be in crowded spaces, and if they are going to be in crowded spaces to use a mask so that they’re protected from respiratory infection.”

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Black and Latinx AML Patients | The Impact of Cultural Beliefs

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Transcript: 

Lisa Hatfield:

Dr. Taveras, can a bone marrow biopsy be used to monitor response to treatment in AML, and are there other tests to help monitor treatment and kind of a unique question, are there any specific dietary or lifestyle recommendations for patients undergoing a bone marrow biopsy or diagnosed with AML?

Dr. Sara Taveras Alam:

Well, the response to treatment in AML is measured with a bone marrow biopsy as the best test to assess response; however, we can have a clue into the response based on the blood test for the patient, so typically patients with acute myeloid leukemia will have anemia and thrombocytopenia, so low hemoglobin, low platelets and will likely be needing transfusions for this. 

Sometimes patients with acute myeloid leukemia will have an elevated white blood cell count or low white blood cell count. Ideally, if a patient has responded to treatment, we would see the hemoglobin and platelets improving and less transfusion requirements. They might not normalize that, they would usually improve if there is response to treatment, and similarly, when it comes to the white blood cells, if the patient has responded to treatment, ideally the white blood cell count should normalize and you should not be seeing any abnormal immature blood cells in the blood work, so we should not be seeing any blasts and ideally we would be having…I’m sorry, a good number of healthy white blood cells.

So that is a surrogate marker for the bone marrow biopsy to assess response, how is the patient doing? What symptoms are they having? What is their CBC or blood count looking like? Ultimately, the bone marrow biopsy is the best test, because then we look at the place where the blood cells are being born and confirm that the blast count has been eradicated, that we see no blasts or at least less than 5 percent, which would be what we call a morphologic remission, then we do deeper assessments by sending the tests about the karyotype or chromosomes that are driving the disease and the mutations that could be driving the disease.

Ideally, if the patient has a very good response, all of those should be gone, sometimes the mutations are still there, but we’re not seeing the deceased being active, and really the bone marrow biopsy will guide the treatment to see if we’re in the right trajectory, if we can continue whatever treatment the patient is on or if we need to switch gears and treat with a different regimen to get the disease back in control.

As it relates to specific dietary or lifestyle recommendations for patients undergoing bone marrow biopsies, I wouldn’t say that there are any specific recommendations for that. On occasion, if a patient is on a blood thinner, they may be asked to stop the blood thinner for the bone marrow biopsy. Of course, that depends on what the indication for the blood thinner is. But in terms of dietary lifestyle changes, I don’t think that any change is necessary.

In terms of patients overall going through acute myeloid leukemia in terms of lifestyle recommendations, it is recommended that the patient be extra careful with infections because they are at higher risk for infection and this may mean different things at different stages of treatment and may be guided by what blood counts are looking like, specifically the neutrophils, which are the healthy white blood cells that help protect us from infections.

So patients that are neutropenic, meaning have low neutrophil count are at really high risk of infections, and we recommend for them to avoid undercooked meat or raw seafood, for example, ceviche or sushi. Any meat should be well cooked and any vegetables have to be very clean, very washed, so that we eliminate the risk of infection.

Oftentimes, I tell my patients to stick to cooked vegetables rather than raw because, unfortunately, if there is some bacteria, then the risk for our patients is much higher than the general population. Additionally, in terms of going out in the world, I would avoid for our AML patients to be in crowded spaces, and if they are going to be in crowded spaces to use a mask so that they’re protected from respiratory infection.

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AML Clinical Trial Participation Disparities | Impact on Access, Outcomes, and Inclusion Strategies

AML Clinical Trial Participation Disparities | Impact on Access, Outcomes, and Inclusion Strategies from Patient Empowerment Network on Vimeo.

What are AML clinical trial disparities, outcomes, and solutions for inclusion? Expert Dr. Sara Taveras Alam from UTHealth Houston discusses patient factors that impact access, underrepresented patient groups, and patient advice for improving clinical trial access. 

[ACT]IVATION Tip

“…inquire if there are clinical trials available at the institution where you’re being cared for, not all institutions do have clinical trials available, and that is okay, but you should be informed and given the opportunity to look into other facilities if clinical trials are available and have the ability to do so.”

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Transcript: 

Lisa Hatfield:

Dr. Taveras, so this is kind of a three-part question regarding disparities in acute myeloid leukemia. So what are the disparities in clinical trial participation among AML patients, and how do these disparities affect access to innovative treatments and outcomes, and then kind of a third part to this question, how can efforts be made to increase diversity and inclusion and clinical trials for AML? 

Dr. Sara Taveras Alam:

Thank you. This is a very important question. Unfortunately, disparities exist in the outcome of AML patients based on different factors, social-economic factors, racial factors, ethnicity, and unfortunately, it has been proven that in clinical trials, the non-Hispanic white population is the predominant population study, so unfortunately, our African Americans or Black patients and our Hispanic patients are underrepresented, and this may impact whether or not the treatments that are getting put, being studied and being utilized in AML patients are appropriate for these patients who were not included on the clinical trials.

I do see that there is an intentional effort to recruit patients from minority groups in institutions where trials are available; however, one caveat is that unfortunately, some of those underrepresented populations don’t necessarily have access to the institutions that are leading the clinical trials. I’m in Houston, and we actually have a county system here in Houston, where leukemia trials are available, and that is really a blessing, because it’s not something that is very common. So throughout my training, when I did go to a county hospital, I was able to see Hispanic patients and African American patients being given the opportunity to participate in clinical trials that may impact the long-term treatment of other patients and those treatments being studied in the population that was using them.

My activation tip for this question is to inquire if there are clinical trials available at the institution where you’re being cared for, not all institutions do have clinical trials available, and that is okay, but you should be informed and given the opportunity to look into other facilities if clinical trials are available and have the ability to do so.

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How Is AML Care Impacted by Bone Marrow Biopsy Results? 

How Is AML Care Impacted by Bone Marrow Biopsy Results? from Patient Empowerment Network on Vimeo.

What is the impact of bone marrow biopsy results on AML care? Expert Dr. Sara Taveras Alam from UTHealth Houston shares how test results are weighed along with patient factors to set a treatment plan and discusses additional patient monitoring, relapse, and how treatment journeys may vary.

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Transcript: 

Lisa Hatfield:

Dr. Taveras, how does the information gathered from a bone marrow biopsy influence treatment decisions for AML care?

Dr. Sara Taveras Alam:

The information gathered from bone marrow biopsies is crucial to decide on the optimal treatment for our patients. We do take into consideration patient factors such as age, comorbidities, and fitness to decide on the treatment that the patient benefits from; however, they are leukemia specific factors, mainly the driving forces behind that leukemia and mutations that may prompt us to use one treatment or another,  so that initial diagnostic bone marrow biopsy is crucial to get the patient started on a treatment course, and then typically, three to four weeks after starting treatment, patients would require what is called a post-induction bone marrow biopsy, so that we can assess the response to treatment, so at that second biopsy, what we’re hoping to see is a patient in a remission, whereas the initial biopsy for an AML patient may have had more than 20 percent blasts or immature cancer cells of AML. 

Our goal is that at this end of induction, three to four weeks after starting chemo, the bone marrow shows less than 5 percent blasts, and then we would call that a morphologic remission. In addition, we would be obtaining the chromosome analysis and mutation testing again on those marrows after treatment, because we would love to achieve the highest response possible where we not only eliminate the bad cells, but we are eliminating the driving forces of these bad cells.

So in an ideal situation where our induction treatment does lead into a remission, AML patients still need to undergo what we call consolidation chemotherapy to maintain a remission. Unfortunately, we know that if we stop treatment, our patients with AML will relapse, and the maintenance treatments depending on the regimen, we may have a stop day at four months or six months, depending on the regimen used, and at different time points during the treatment, a bone marrow biopsy may be repeated.

I think the most crucial time for bone marrow biopsies are at the diagnosis and after induction, if we have achieved our goal to achieve remission, then the bone marrow biopsy may be repeated monthly, depending on the institution that the patient is going to.

However, that part is negotiable depending on the patient’s goals and wishes. If the patient were planned for a stem cell transplant because of the characteristics of their leukemia…if it’s a more aggressive type of acute myeloid leukemia, what we call intermediate or poor risk acute myeloid leukemia, a stem cell transplant is recommended, and before proceeding with a stem cell transplant, we must confirm that the patient continues to be in a remission, so that’s another crucial time point to repeat the bone marrow biopsy in addition to the beginning of induction, so they’re getting a diagnosis and the end of that first induction treatment.

The time points between those two are kind of negotiable, especially in patients that have a lot of trouble with the biopsies, but may be very beneficial to confirm that we are keeping the patient into remission and carry the prognosis of the patient.

Of course, if there’s any concern that there’s a relapse, that would be another reason to repeat a bone marrow biopsy, and while confirmed that there has been a relapse and see what characteristics of the AML has changed, and what treatment would be appropriate at that time frame. Once a patient has been in remission, completed their maintenance treatment potentially received a stem cell transplant if it was appropriate for them, usually patients are surveillance clinic followed up, and a bone marrow biopsy is advisable for their first few years, about every three months to confirm that we’re maintaining a remission and that no further action is needed.

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AML Diagnosis | Exploring Bone Marrow Biopsy and Alternatives

AML Diagnosis | Exploring Bone Marrow Biopsy and Alternatives from Patient Empowerment Network on Vimeo.

What are the purpose and alternatives to bone marrow biopsy? Expert Dr. Sara Taveras Alam from UTHealth Houston explains what’s involved in bone marrow biopsy, what is analyzed, patient advice for the procedure, and alternative testing methods.

[ACT]IVATION Tip

“…ask the providers what to expect from the bone marrow in the facility where you are in. Usually in all facilities, lidocaine, or local anesthesia is used, but if you foresee that in general, you are anxious about procedures or susceptible to pain, you are welcome to request for some medications for pain and anxiety to help you get through that procedure, and generally, once patients have undergone a first bone marrow biopsy, they know what to expect and what accommodations may be needed for them in subsequent bone marrow biopsies.”

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Transcript: 

Lisa Hatfield:

Dr. Taveras, what specific features are pathologists looking for in the bone marrow sample when diagnosing AML, and are there any alternative diagnostic methods or tests available for AML besides a bone marrow biopsy?

Dr. Sara Taveras Alam:

And that is a great question. I think that many patients may be scared of what bone marrow biopsy entails. It is a procedure after all, and it can be painful. I do know that they’re able to get some details about the diagnosis from the peripheral blood just from blood tests alone; however, the best diagnosis is performed through the bone marrow biopsy, so it can provide more information about the email, than what we’re able to obtain from the blood, sometimes the blood count, the white blood cell counts are elevated in AML and that may make it easy to do some of our testing from the blood work, but in other patients, the white blood cells may be low at presentation and that can make it very difficult to obtain any meaningful diagnostic and prognostic information without a bone marrow biopsy.

The bone marrow biopsy would also allow to tell if the patient had a preceding blood disorder like a myeloid dysplasia and this may have treatment implications. This is not something that we would be able to tell from the blood alone unfortunately, so when our pathologists look at the bone marrow sample, they are looking at some of the blood that is obtained from that boom marrow space where the blood is produced, and a tiny piece of the bone from there as well, and they’re looking at the amount of cells, especially the normal red cells, the normal white blood cells, normal platelets, and specifically the abnormal white blood cells or blasts that are quantified in a percentage fashion to diagnose the AML.

There are also different types of blasts, so they may be able to sub-classify the AML from just looking at the morphology or how these cells look under the microscope. There are many ancillary tests that are performed on the sample as well to look into the genetics for the driving forces behind the acute myeloid leukemia.

We look at a chromosome analysis to see what the chromosomes are for the leukemia. We look at mutations during FISH testing, and we do molecular testing that are looking at specific point mutations that may be associated with AML and provide insight into the treatment options as well as the prognosis, the patient’s disease, and whether or not they may benefit from a stem cell transplant to increase the chances of maintaining a remission and obtaining a cure.

My advice for patients who may be anxious about the bone marrow biopsy would be to voice their concerns for their providers. I believe that different centers have different practices as it relates to pre-medication, so some places may provide anxiety medications and pain medications in advance of the procedure, but some other facilities may not. So my activation tip for this question is to ask the providers what to expect from the bone marrow in the facility where you are in.

Usually in all facilities, lidocaine, or local anesthesia is used, but if you foresee that in general, you are anxious about procedures or susceptible to pain, you are welcome to request for some medications for pain and anxiety to help you get through that procedure, and generally, once patients have undergone a first bone marrow biopsy, they know what to expect and what accommodations may be needed for them in subsequent bone marrow biopsies.

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Advancements in AML Treatment | Tailoring Therapies to Individual Patients

Advancements in AML Treatment | Tailoring Therapies to Individual Patients from Patient Empowerment Network on Vimeo.

What are the latest AML treatment advancements? Expert Dr. Sara Taveras Alam from UTHealth Houston discusses how treatments have advanced over recent years with personalized therapies beyond a one-size-fits-all approach.

[ACT]IVATION Tip

“…patients to be really informed about all of the details of their AML and ask questions about the genetic drivers of their disease and whether or not there are medications that can target those drivers. Similarly, the decision to do a stem cell transplant or not will be driven by this, so it’s very important for the patient to be informed about all of the details of their AML, not just the fact that they have acute myeloid leukemia diagnosis.”

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Transcript: 

Lisa Hatfield:

Dr. Taveras, what are the latest advancements and treatment modalities for AML?

Dr. Sara Taveras Alam:

Well, over the last decade, there have been many new medications approved for the treatment of AML, and this has really allowed for the treatment of acute myeloid leukemia to be individualized rather than using a one-size-fits-all approach, so typically for us to decide the treatment that best suits the patient, we take into consideration patient characteristics and into consideration, their age and their fitness level, other medical problems that they may have, and we also take into consideration characteristics of the leukemia itself, so not all acute myeloid leukemia are the same, and we try to get as much information as we can about what is driving the acute myeloid leukemia to see how we can best attack it.

One of the medication groups that we have available to us over the last decade are FLT3 inhibitors, and that is a class of medication that directly targets FLT3 mutations that may be present in patients with AML, and if the patient does have a FLT3 mutation and they’re able to be started on this class of medication, they do a lot better than they would have done, say, 20 years ago without those medications being available. Similarly, we have medications that target IDH mutations, IDH1 or 2 that are options for our patients. We have less intensive chemotherapy that is more appropriate for older patients with comorbidities, perhaps maybe more tolerable than the traditional IV intensive chemotherapy.

So my activation tip for this question is for patients to be really informed about all of the details of their AML and ask questions about the genetic drivers of their disease and whether or not there are medications that can target those drivers. Similarly, the decision to do a stem cell transplant or not will be driven by this, so it’s very important for the patient to be informed about all of the details of their AML, not just the fact that they have acute myeloid leukemia diagnosis.

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The Importance of Acute Myeloid Leukemia Patient Empowerment

The Importance of Acute Myeloid Leukemia Patient Empowerment from Patient Empowerment Network on Vimeo.

Why is acute myeloid leukemia (AML) patient empowerment vital? How can acute myeloid leukemia (AML) patients become empowered? AML expert Dr. Catherine Lai from Penn Medicine explains how she helps empower her patients and why educating patients is a vital part of their care.

[ACT]IVATION TIP from Dr. Lai: “Don’t be afraid to ask questions, don’t be afraid to ask about resources and other ways to get information, you want the right resources, so not necessarily…everything on Google is accurate, but there are lots of good resources out there that can give you the information needed so that you can make educated decisions.”

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Transcript: 

Dr. Lai: 

It’s important to empower patients so that we’re making the best decision for them…that’s in line with their goals. I think that one of the main reasons why I love what I do is because I’m able to participate in the patient’s journey, and that journey doesn’t always mean that a patient has to live longer.

So I try to ask patients or do as patients, what are their…short- and long-term goals, do they have life events that they want to get to, is there a wedding coming up, a grandchild or something that I can help them get them to so that we can make a decision together that is taking into consideration their life outside of clinic and outside of the hospital.

I like to try to spend a lot of time with my patients educating them. Some people say I sometimes give them too much information, but I don’t feel like patients can make good decisions without being properly informed. So an educated patient makes a much better…makes a much better decision than somebody who doesn’t have the information.

And then I would also say it’s important to emphasize that you and your provider and our advanced practice provider and the social worker, we’re all a part of the same team that we all want the best outcome for the patient. And so knowing that, that you have a team of people that are taking care of you and that you really need to embrace learning and understanding as much as possible so that you can make the best decision about your short-term and long-term plan for yourself. So activation tip here is don’t be afraid to ask questions, don’t be afraid to ask about resources and other ways to get information, you want the right resources, so not necessarily…everything on Google is accurate, but there are lots of good resources out there that can give you the information needed so that you can make educated decisions.

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What AML Mutations Are Associated With Adverse Outcomes?

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

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

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

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?

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

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

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.”

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Transcript: 

Art:

Dr. Daver, what is the importance of clinical trial participation as it relates to breakthroughs in AML, and what advice do you have for AML patients considering a clinical trial?

Dr. Naval Daver: Clinical trials are critical for the progress that we have already seen an acute myeloid leukemia, the drugs that have been improved in the last six, seven years, including venetoclax (Venclexta), FLT3 inhibitors, midostaurin (Rydapt or Tauritmo),  gilteritinib (Xospata), hopefully quizartinib other emerging targeted therapies…IDH1, IDH2 inhibitors, menin inhibitors, CD47 antibodies, we’ve learned about all of them and have got approvals and many of them through the ongoing clinical trials.

I think it’s very important for patients to realize that in most large academic centers, we will only participate in the clinical trial if we think it has the potential to improve the standard of care in the future. There’s very little incentive for academic investigators or clinical investigators, such as myself, we’re very, very busy to get involved in a trial if we don’t think that it has the potential to improve the outcome or change the nature of AML therapy in the future, so a lot of patients often ask me, Oh, I want the randomized or placebo arm. There is no real placebo alone in any AML study that I’m aware of, most of the studies will use standard of care, which is what you would’ve gotten wherever you were getting treatment at home, locally, community hospital versus a standard of care plus where the new drug will be added, whether it’s the FLT3 inhibitor, the CD47 antibody, the menin inhibitor 

So there’s a good chance, 50 percent that you’re going to get standard of care plus that we think has the potential to improve the outcome, of course, you never know, that’s what you do, the trial, but we think based on the previous pre-clinical data to pass when the page to deliver this looks like it will improve the outcome for this molecular or site group versus standard of care, which is what you will have gotten.

So I think it’s important to realize that you will never get less on standard of care and any clinical trial, at least in the AML field, and at least in our experience that they understand. 

Now, beyond that, there’s also a Phase I in two states, and those are the ones that we focus on quite a bit at MD Anderson, these are single arm studies, meaning everybody will get the investigational agent combo, so azacitidine (Onureg or Vidaza) and venetoclax (Venclexta), we were one of the first sites to work on and leave this study and all of our patients in 2015, 2016, we’re getting this regiment, it was not approved to much later in 2019, 2020, and for those three, four years, our patients, hundreds of patients were able to get that combination, which probably cured many, many more than would have been cured to the standard of care until, of course, I’ve got a pro four years later, but for an option, of course, you cannot wait four years, so I’m a huge believer in clinical trials, I think it’s really, really important, both for the patients themselves as well as for the field, for us to be able to move the entire AML field forward for the next decade, and I would very strongly consider looking at or discussing with your treating physician trial options, and then you can look at them on your own through clinicaltrials.gov, or other sites with leukema and lymphoma that give a lot of information on clinical trials. 

So my activation tip related to this question is that I think 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, all of the clinical drug approvals in progress we have seen in AML in the last six, seven years have come through clinical trials that patients in the past have agreed to kindly participate and helped probably themselves by getting better medications and combinations, and definitely the field to move forward, so definitely a big proponent for clinical trials. 

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A Look at Treatment Strategies for High-Risk AML Patients

A Look at Treatment Strategies for High-Risk AML Patients from Patient Empowerment Network on Vimeo.

What acute myeloid leukemia (AML) treatments are available for high-risk patients? Dr. Naval Daver from the University of Texas MD Anderson Cancer Center discusses various mutations, potential for cure, and clinical trials. Learn about the outlook for high-risk AML treatments.

[ACT]IVATION TIP from Dr. Daver:The best way to get up to these agents is to go on clinical trials and incorporate these therapies, both in the frontline setting as well as in the relapsed refractory setting.” 

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Transcript: 

Art:

Dr. Daver, what treatment strategies are available for high-risk AML patients?

Dr. Naval Daver:

High-risk AML patients includes a group of a number of different mutations, and cytogenetic abnormalities, this includes TP53 mutation, as well as adverse cytogenetics, which includes chromosome 17, deletion 5, deletion 7, as well as complex carrier type. This entire group historically had a poor outcome and has had limited responses to traditional intensive chemo, even if we achieve responses there, usually short-lived.

We do have some patients where we are able to achieve remission with intensive chemo or with azacitidine-venetoclax (Vidaza-Venclexta) and transition and transmission them transplant with about 25 to 30 percent potentially achieving a long-term remission and possible cure. 

But aside from that, there is very little potential to cure these patients with just traditional intensive chemo, venetoclax in this area, there has been developments with the emergence new class of immunotherapy drugs, called CD47 antibodies, the one that’s most advanced in this field is a drug called magrolimab, and we are evaluating the drugs such as magrolimab in combination with azacitidine as well as in combination with azacitidine-venetoclax and are seeing high remission rates, both in TP53 mutated and TP53 wild type.

So this pathway that works by activating a macrophages or the immune system to attack the tumor cells, seems to be in some way mutation agnostic with response rates being maintained even in the traditional high-risk subsets, especially such as TP53 and complex cytogenetics for some of the other high-risk groups such as MLL, we’re using targeted therapies like menin inhibitors, and these seem to work well in those patients who have these adverse cytogenetic molecular abnormalities, so there is progress, and we think that the CD47 antibody field and hopefully the main inhibitor feed will be able to improve outcomes in these traditionally molecular cytogenetic subsets.

My activation point related to this question is for high-risk mutations and cytogenetic commonalities such as TP53 complex carrier chromosome 17 MLL,  best hope at this time is in clinical trials evaluating novel therapies such as CD47 antibodies and menin inhibitors. These are not yet FDA-approved, but based on emerging data from the ongoing Phase I, II studies, we think that there is a good chance they will be approved in the future.

However, this time, the best way to get up to these agents is to go on clinical trials and incorporate these therapies, both in the frontline setting as well as in the relapsed refractory setting. 

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