Tag Archive for: menin inhibitors

What AML Mutations Are Associated With Adverse Outcomes?

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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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What Does Triplet Therapy in AML Mean for the Future?

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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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AML Clinical Trials Critical to Treatment Breakthroughs and Improvements

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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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Why Is the Menin Pathway Important in AML?

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Why Is the Menin Pathway Important in AML? from Patient Empowerment Network on Vimeo.

What should acute myeloid leukemia (AML) patients know about the menin pathway? Dr. Naval Daver from the University of Texas MD Anderson Cancer Center shares information from ASH 2022. .Learn research updates about the menin pathway and ongoing clinical trials on the pathway.

[ACT]IVATION TIP from Dr. Daver: “Patients should be checked for arrangements like MLL rearrangement NPM1 mutation, new fusions as these may be amenable to therapy with the menin inhibitors, there are multiple trials with five different menin inhibitors, single agent trials and also combination trials now ongoing across multiple centers both in the U.S. and ex-U.S.“

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Transcript: 

Art:

Dr. Daver, what is a menin pathway in AML? And why is it significant?

Dr. Naval Daver:

The menin pathway is very recently discussed that way, the pathway, of course, itself has been known for almost a decade, this is an epigenetic pathway, and in certain subsets of AML such as MLL rearranged NPM1 mutated as well as other fusions, we find that there is an up regulation of the menin impact rearrangement, and this actually results in increased production of two enzymes called meis-1 and hox-DNA) these enzymes actually result in a differentiation blockade. So normally, in the bone marrow we have the early progenitor cells, this then leads to be a report cell and leads to mature neutrophils and monocytes and blood cells, but in a differentiation blockade, we would see that those cells over time would start generating mutations and become leukemic cells.

So one of the most physiological ways to treat AML is to actually remove the differentiation blockade, so the normal process of differentiation with progress, and so these menin inhibitors are able to reduce the levels of MEIS1 and HOXA by doing this, they allow the normal differentiation cascade to progress, and they’re not cytotoxic targeted chemo, they’re not directly killing leukemia, but they’re actually allowing the leukemia itself to then mature to no monocytes and neutrophils.

And so now there are five different menin inhibitors in ongoing clinical trials, but two of these are more advanced and have shown data recently in the ASH 2022 meeting the newer drugs, and are showing close to 40 to 50 percent single agent efficacy, and we believe that after the FLT3, IDH1, IDH2 inhibitors, which have been approved in the last five years, the menin inhibitors are probably the next other targeted therapies that will hopefully get approval and they eventually be used in the frontline setting in combination approaches. 

The activation tip related to this question is that patients should be checked for arrangements like MLL rearrangement NPM1 mutation, new fusions as these may be amenable to therapy with the menin inhibitors, there are multiple trials with five different menin inhibitors, single agent trials and also combination trials now ongoing across multiple centers both in the U.S. and ex-U.S., and if one does have an aberration that will be sensitive to such menin inhibitor-based therapy, I would strongly recommend considering trying to get on one of those trials because we believe that these will be the best outcomes with such standard therapies rather than using the standard or traditional chemotherapies. 

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AML Treatment Approaches Expand for Older and High-Risk Patients

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AML Treatment Approaches Expand for Older and High-Risk Patients from Patient Empowerment Network on Vimeo.

How have acute myeloid leukemia (AML) treatment approaches expanded for older and high-risk patients? Dr. Naval Daver from the University of Texas MD Anderson Cancer Center shares insight about additional treatment options. Learn about the potential for long-term cures for these patient groups. 

[ACT]IVATION TIP from Dr. Daver: “There is a dramatic progress, especially in the treatment of older unfit AML with the approval of the azacitidine-venetoclax combination.”

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Transcript: 

Art: 

Dr. Daver, for older and high-risk AML patients, how are the treatment approaches expanding?

Dr. Naval Daver: 

In older and high-risk AML, the major approval has been the combination of azacitidine (Onureg or Vidaza) and venetoclax (Venclexta), which is a BCL-2 inhibitor, the regimen was evaluated in a large Phase III study called the VIALE study, where we looked at the standard of care for the last two decades for older unfit AML, which azacitidine alone versus the combination of azacitidine and venetoclax and this combination showed a three times higher remission rate, 75 versus 28 percent overall remission rate as well as an improvement in overall survival and long-term survivors.

So this has led to great progress with now remission rates of 75 percent achievable in older unfit AML and many of them being durable at three years with ongoing follow-up, so this has really opened the door for us to be able to treat patients up to 75, 80, 85 years of age with effective therapy given the three parts of these to achieve remission, which is usually associated with freedom from transfusion improvement, quality of life, improved energy, less time in the hospital, less infections.

The other progress now is coming from the use of targeted therapies as well in these populations, and even though the HMA venetoclax or azacitidine combination is doing very well.

We now have data, in fact, from the ASH 2022 December meeting that at three years, about 25 percent or so I would still remain alive with azacitidine was even or 8 percent, now it’s 25 percent. But, of course, we want to do much better than that, and so this is where we are incorporating the targeted therapies, the FLT3 inhibitors, the IDH1, IDH2 inhibitors, menin inhibitors, and immunotherapies onto the backbone of azacitidine-venetoclax, which we hope will further improve that long-term survival cure from 25 to hopefully 50 to 60 percent and beyond.

So a lot of progress, you know, going from less than 10 percent, a 30 percent survival, long-term, and I think in the next few years, even up to 50 percent with some of these new combinations. The activation tip related to this question is that there is a dramatic progress, especially in the treatment of older unfit AML with the approval of the azacitidine-venetoclax combination.

This regimen is now giving high remission rates, which approximate remission rates that are seen with traditional intensive chemotherapy without the mucositis and toxicities and better volatility, and we are now working to further improve the remission and the durability of this dominant of initial.

 …potentially adding targeted therapy such as FLT3 inhibitors, IDH1, IDH2 menin inhibitors, and we think that potentially in the next decade, we could be achieving long-term cures in a large proportion of older unfit AML, which was something one could just dream of a decade ago. 

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What Promising AML Treatments Are Available for Newly Diagnosed Patients?

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What Promising AML Treatments Are Available for Newly Diagnosed Patients? from Patient Empowerment Network on Vimeo.

What do newly diagnosed acute myeloid leukemia (AML) patients have for promising treatment options? Dr. Naval Daver from the University of Texas MD Anderson Cancer Center discusses progress in available treatments. Learn about therapies determined by key factors.

[ACT]IVATION TIP from Dr. Daver: “It’s very important to really consider all the available treatment options and if needed to seek consultation with an expert or academic center to get the most up-to-date treatments available for AML.“

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Transcript: 

Art:

Dr. Daver, for newly diagnosed AML patients, what are the latest and most promising available therapies?

For newly diagnosed AML at this time, the most promising agents include targeted therapies and BCL-2 inhibitor treatments, these are non-chemotherapeutic drugs, and we’ve seen great progress in the application of these as well as recent FDA approvals.

So one of these is an agent called venetoclax (Venclexta), which is a BCL-2 inhibitor and venetoclax in combination with hypomethylating agents such as azacitidine (Onureg or Vidaza) has shown a response to close to 75 percent. 

And the nice thing is that this regimen can be given and patients who are older than 70, 75 years of age, and even those who are having comorbidities are not fit for traditional intensive chemotherapy with similar response rates, so this has been approved in the last couple of years for the frontline treatment of AML, and we’ve been using this combination of venetoclax and azacitidine quite frequently with high efficacy in this patient population, the other new agents that have shown breakthroughs in AML are the targeted therapies, these include FLT3 inhibitors that target the FLT3 mutation and these have shown good activity, but the single agents with gilteritinib (Xospata) being approved in the relapsed refractory setting as a single agent where gilteritinib showed a response rate of about 50 percent as a single oral targeted therapy in relapsed FLT3-mutated AML, which is actually better than the response rate with high-dose combination more where the response rate is only about 25 to 30 percent.

So, gilteritinib is now approved, and it’s now moving and being evaluated in frontline setting other FLT3 inhibitors like lestaurtinib (CEP-701), actually just recently completed frontline studies showing improved outcome when lestaurtinib added to intensive chemo versus just intensive chemo in FLT3 in AML. And we hope and think there’s a good chance lestaurtinib will be approved in the near future.

And also IDH inhibitors have been approved both in the relapsed setting, frontline setting, and now we even have a third group of targeted therapy is called the menin inhibitors, they target MLL rearrangement and NPM1 mutations, which are seen in about 15 percent to 20 percent of the AML, so there’s been a lot of progress.

All of this in the last seven years, six, seven years with multiple targeted therapies, with multiple inhibitor-based treatments, showing progress in AML and then also recently, the concept of maintenance therapy, this is something we used for the last couple of decades in a acute lymphoblastic leukemia and multiple myeloma and in lymphoma.

But we had not had clear data in AML, but the recent study using oral formulation of a azacitidine in CC486 has shown the maintenance in patients who complete an induction consolidation and could not go to allogeneic stem cell transplant for one reason or the other was important and improve both overall survival and relapse-free survival, and so this is the first time now we have an FDA-approved and standard use of maintenance therapy after the traditional induction consolidation, so even changing the general paradigm of AML therapy.

So a lot has changed in the last seven to eight years in the treatment of acute myeloid leukemia, and this is very exciting.

And the activation tip related, this question is that there are multiple new targeted and low intensity therapeutic options available for patients with acute myeloid leukemia, and in our institution, in my opinion, even older patients are eligible for some form of therapy or the other…very few patients, if any, today, are being sent to hospitals or palliative care without treatment.

So it’s very important to really consider all the available treatment options and if needed to seek consultation with an expert or academic center to get the most up-to-date treatments available for AML. 

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How Does the Presence of Molecular Markers Affect AML Care?

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How Does the Presence of Molecular Markers Affect AML Care? from Patient Empowerment Network on Vimeo.

Dr. Farhad Ravandi-Kashani reviews how the presence of gene mutations can influence acute myeloid leukemia (AML) treatment choices and discusses new molecular markers being researched for future AML care.

Dr. Farhad Ravandi-Kashani is professor of medicine and Chief of the Section of Developmental Therapeutics in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, TX. Learn more about Dr. Ravandi-Kashani.

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Transcript:

Laura Beth:

How do test results impact AML care and treatment decisions?  

Dr. Ravandi:

So, in the first place, the presence or absence of certain mutations can be predictable outcome. Some subsets of leukemias are, for the lack of a better term, more favorable.  

I personally don’t think there is anything favorable about any leukemia, but some are easier to treat, and some are easier to cure than others. There is one specific subtype called acute promyelocytic leukemia that we actually completely treat differently. We don’t use even chemotherapy in that subset of leukemia.  

It has almost 100 percent success rate. And the treatment of other subsets can also be tailored, depending on these molecular and chromosomal changes. So, the initial therapy can be actually changed. There are now, for example, targeted agents that can be added to the chemotherapy, during initial chemotherapy.  

And also, once the patient is in remission, depending on favorable or unfavorable their leukemia is, they may be offered allogeneic stem cell transplant. So, yes, this information is highly important. In fact, I would say crucial for our decision-making in leukemia therapy these days.  

Laura Beth:

So, what is new in AML research related to molecular markers?  

Dr. Ravandi:

Well, it depends on your definition of new, but FLT3 mutations are very important because they’re now several FLT3 inhibitors, and as I mentioned, the initial therapies are different, to some extent. The IDH mutations are very important, again, because they are specific targeted agents.  

TP53 mutations are important because, unfortunately, they are particularly unfavorable.  

This is completely hot off the press, but there are subsets of AML called MLL rearranged leukemias that can respond to these drugs called Menin inhibitors.  

There are other mutations that have been discovered, many other ones, that there are no specific treatments for at the moment, but there’s a lot of research on.  

How Do Gene Mutations Affect AML Treatment Choices?

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How Do Gene Mutations Affect AML Treatment Choices? from Patient Empowerment Network on Vimeo.

Dr. Eytan Stein shares why AML patients should undergo molecular testing when choosing a treatment approach, explaining how targeted therapy works to treat AML patients who have specific genetic mutations.

Dr. Eytan Stein is a hematologist oncologist at Memorial Sloan Kettering Cancer Center and serves as Director of the Program for Drug Development in Leukemia in Division of Hematologic Malignancies. Learn more about Dr. Stein, here.

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Transcript:

Katherine Banwell:

Why is identification of genetic markers essential before choosing treatment?  

Dr. Eytan Stein:

Because when you know the genetic markers, you can target the genetic abnormalities, sometimes with specific targeted therapies, with therapies that fit like a key in a specific lock.  

And those targeted therapies have been shown, in some cases, to improve the survival of the patients, without much cost, without much toxicity. So, I’ll give you an example of this.  

There is a very common genetic abnormality in patients with acute myeloid leukemia called the FLT3 or FLT3 mutation. When you have that mutation, there is a targeted therapy that targets the FLT3 mutation called midostaurin (Rydapt), and it’s been shown in a very large clinical trial that the addition of the targeted FLT3 inhibitor midostaurin in combination with chemotherapy leads to better overall survival than chemotherapy alone.  

So, you need to know that information because you want to give your patient the best chance at beating the disease. And that’s why it’s also important to try to get this information back quickly. You know, no one wants to be sitting around waiting for four weeks to find out if they’ve got a specific mutation. And we’ve gotten better. I think medical centers generally have gotten better at getting this mutational information back to their doctors relatively quickly. 

Katherine Banwell:

Does every patient get this standard testing? 

Dr. Eytan Stein:

It is – does everyone get it? I don’t know. But “Should everyone get it?” is, I think, the important question. Yes, everyone should get this testing.  

It is incorporated into the NCCN and National Comprehensive Cancer Network and European Leukemia Net guidelines. It is important not only because you can think about targeted therapies, but it is also important for prognostic reasons, meaning that certain mutations lead to a higher risk of relapse, and those mutations in a patient might lead me to recommend a stem cell transplant, which is sort of the most intensive thing we can do to help prevent a relapse, while other mutations, which might be “favorable”, in quotes, they might lead me not to recommend a stem cell transplant.  

So, I think this mutational testing is the standard of care and should be done in every patient with newly diagnosed acute myeloid leukemia.  

What Are Current and Emerging AML Treatment Approaches?

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

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

Dr. Eytan Stein is a hematologist oncologist at Memorial Sloan Kettering Cancer Center and serves as Director of the Program for Drug Development in Leukemia in Division of Hematologic Malignancies. Learn more about Dr. Stein, here.

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Transcript:

Katherine Banwell:

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

Dr. Eytan Stein:

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

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

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

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

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

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

Katherine Banwell:

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

Dr. Eytan Stein:

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

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

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

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

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

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

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

Katherine Banwell:

Where do clinical trials fit in to all of this? 

Dr. Eytan Stein:

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

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

Katherine Banwell:

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

Dr. Eytan Stein:

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

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

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

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

Thriving With AML: What You Should Know About Care and Treatment

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Thriving With AML: What You Should Know About Care and Treatment from Patient Empowerment Network on Vimeo.

What should you consider when choosing acute myeloid leukemia (AML) care and treatment? Dr. Eytan Stein reviews factors that help guide care decisions for AML, discusses the goals of treatment as well as treatment options available, and shares tools for taking an active role in your care.

Dr. Eytan Stein is a hematologist oncologist at Memorial Sloan Kettering Cancer Center and serves as Director of the Program for Drug Development in Leukemia in Division of Hematologic Malignancies. Learn more about Dr. Stein, here.

See More from Thrive AML

Related Resources:

Thriving With AML: What You Should Know About Care and Treatment Resource Guide

 Shared Decision-Making, Advice for Partnering With Your AML Team

 Which Tests Do You Need Before Deciding on an AML Treatment Path

Transcript:

Katherine Banwell:  

Hello, and welcome. I’m Katherine Banwell, your host for today’s webinar. Today’s program is about how to live and thrive with AML. We’re going to discuss the goals of AML treatment and how you can play an active role in your care. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining us is Dr. Eytan Stein. Dr. Stein, welcome. Would you please introduce yourself?  

Dr. Stein:

Thanks so much. My name is Eytan Stein. I work as an attending physician on the leukemia service at Memorial Sloan Kettering Cancer Center in New York City.  

Katherine Banwell:

Excellent. Thank you so much for taking the time to join us today. 

Dr. Stein:

Thank you for having me.  

Katherine Banwell:

Since this webinar is part of Patient Empowerment Network’s Thrive series, I thought we could start by getting your opinion on what you think it means to thrive with AML. 

Dr. Stein:

Yeah, so thriving with AML I think can mean different things to different people. Thriving with AML can mean when you have the disease, really having the fortitude to get through the treatment that you’re being given because sometimes that can be tough.  

And sometimes, it’s not easy. But the people who are thriving are the ones who are able to discuss with their doctors what their treatment is, what the side effects of that treatment might be, how to minimize those side effects, and how to get through that treatment so that not only do they feel better physically but can feel better emotionally and ultimately, hopefully go into a complete remission. 

Katherine Banwell:

Thank you for that, Dr. Stein. I think that helps guide us as we continue this conversation. Getting appropriate AML care is part of thriving, and when we consider treatment options, it’s important to understand the goal of treatment. So, how would you define treatment goals for patients? 

Dr. Stein:

Yeah, so the treatment goals for patients really come in different forms. I think fundamentally what everyone wants is everyone wants to go into a complete remission and be cured of their disease. And certainly, that’s an overarching goal that we aim to achieve with our treatments. But there are other goals that I think are important too to various patient populations, depending on what stage of life they’re in.  

Are they 85 years old or 90 years old and have lived a long, full life? And their goal might be to improve their blood count so they don’t need transfusions so frequently. And they might be able to go to that grandchild or great-grandchild’s wedding or other life event. There are other patients for whom the goal might be, very discreetly, just to get to that next step in their treatment.   

That next step in their treatment might be a bone marrow transplant. The next step in their treatment might be some more therapy. But I think overall as a doctor, our goal is always to do our best to get our patients into a complete remission and cure them while maintaining the best quality of life for our patients.  

Katherine Banwell:

What do you think is the patient’s role in setting treatment goals? 

Dr. Stein:

Well, it’s really important for the doctor to explore the goals of treatment when they first meet with the patient. I don’t think doctors should assume that all patients come into that first visit with the same goals. And what those goals are, I think, may differ a little bit from patient to patient. And it’s really important for the patient to express overtly what their goals are, what they want to achieve from the treatment. You know, I have some patients who come in to me and say, “My goal is to be cured and be alive for the next 30 years” or 40 years or 50 years.  

And I have some patients that come into treatment, and they say, “You know what, I have had a very, very long life, and I just want the best quality I can have for as long as I can possibly have it.” 

Katherine Banwell:

Yeah, that’s great advice. Thank you. As we move into the discussion about treatment for AML, let’s define a couple of terms that are often mentioned in AML care. What is induction therapy?   

Dr. Stein:

Yeah, so induction chemotherapy refers really to a type of chemotherapy that tends to be quite intensive, so strong chemotherapy that patients receive in the hospital setting. That induction chemotherapy typically requires a hospitalization of three to four weeks, sometimes a little bit longer, as the patient gets their treatment during the first week or so and then they’re recovering from the effects of that treatment during the next three weeks in the hospital.  

Katherine Banwell:

Okay. What is consolidation therapy? 

Dr. Stein:

Ah. So, a patient first gets induction chemotherapy. If they achieve a complete remission, so their disease goes away, that’s great. We know their disease seems to be gone. But we also know that patients relapse. So, if patients relapse, it means their disease wasn’t really gone. It’s just that we couldn’t find it. It was hiding somewhere.  

So, consolidation chemotherapy is chemotherapy that is given after a patient is in complete remission in an effort to kill any residual leukemia cells that may be hiding in the body, that we can’t see in our bone marrow biopsies, in an effort to deepen the remission that we’ve achieved during induction.  

Katherine Banwell:

Okay. Are there any other terms that patients should be familiar with? 

Dr. Stein:

There are. You know, there are a lot of other terms that patients should be familiar with. I’ll just touch on one because it can get complicated. We now have for acute myeloid leukemia, a type of therapy that goes beyond induction and consolidation called maintenance therapy.  

Maintenance therapy is when a patient is done with induction, done with consolidation, and the question is, can you give them something that is easy to take, relatively non-toxic, that they can take for a prolonged period of time, to also help prevent relapse? Maintenance therapy has been really a backbone of the treatment of a different kind of leukemia called acute lymphoblastic leukemia, which happens primarily in children for many years. Maintenance therapy is also now a backbone of therapy for a different kind of blood cancer called multiple myeloma. And very recently, only within the past year to two years, we’ve incorporated maintenance therapy for AML for certain groups of patients.  

Katherine Banwell:

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

Dr. Stein:

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

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

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

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

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

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

Katherine Banwell:

And we are going to talk further about that in a couple of minutes. What about stem cell transplant? Who might be right for that? Who might be eligible? 

Dr. Stein:

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

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

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

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

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

Katherine Banwell:

We’ll talk about the future in a couple of minutes. 

Dr. Stein:

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

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

Katherine Banwell:

Wow, okay. That’s great. Where do clinical trials fit in to all of this? 

Dr. Stein:

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

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

Katherine Banwell:

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

Dr. Stein:

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

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

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

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

Katherine Banwell:

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

Dr. Stein:

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

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

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

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

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

Katherine Banwell:

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

Dr. Stein:

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

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

Katherine Banwell:

Yeah. Why is identification of genetic markers essential before choosing treatment?   

Dr. Stein:

Because when you know the genetic markers, you can target the genetic abnormalities, sometimes with specific targeted therapies, with therapies that fit like a key in a specific lock. And those targeted therapies have been shown, in some cases, to improve the survival of the patients, without much cost, without much toxicity. So, I’ll give you an example of this.  

There is a very common genetic abnormality in patients with acute myeloid leukemia called the FLT3 or FLT3 mutation. When you have that mutation, there is a targeted therapy that targets the FLT3 mutation called midostaurin, and it’s been shown in a very large clinical trial that the addition of the targeted FLT3 inhibitor midostaurin in combination with chemotherapy leads to better overall survival than chemotherapy alone.   

So, you need to know that information because you want to give your patient the best chance at beating the disease. And that’s why it’s also important to try to get this information back quickly. You know, no one wants to be sitting around waiting for four weeks to find out if they’ve got a specific mutation. And we’ve gotten better. I think medical centers generally have gotten better at getting this mutational information back to their doctors relatively quickly. 

 Katherine Banwell:

Does every patient get this standard testing? 

Dr. Stein:

It is – does everyone get it? I don’t know. But “Should everyone get it?” is, I think, the important question. Yes, everyone should get this testing.  

 It is incorporated into the NCCN and National Comprehensive Cancer Network and European Leukemia Net guidelines. It is important not only because you can think about targeted therapies, but it is also important for prognostic reasons, meaning that certain mutations lead to a higher risk of relapse, and those mutations in a patient might lead me to recommend a stem cell transplant, which is sort of the most intensive thing we can do to help prevent a relapse, while other mutations, which might be “favorable”, in quotes, they might lead me not to recommend a stem cell transplant.   

So, I think this mutational testing is the standard of care and should be done in every patient with newly diagnosed acute myeloid leukemia.  

Katherine Banwell:

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

Dr. Stein:

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

Katherine Banwell:

How often would a patient need to have a biopsy?  

Dr. Stein:

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

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

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

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

Katherine Banwell:

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

Dr. Stein:

Yeah, so when a patient relapses, which unfortunately happens more than we want it to, it’s important No. 1 to do another bone marrow biopsy and at that point, do that mutational testing again because the mutations that are present at the time of diagnosis are not necessarily going to be present at the time of relapse, and sometimes, a new mutation might occur at the time of relapse. And again, what that mutational profile shows can help determine what the next best treatment for the patient is. There might be standard-of-care therapies. More chemotherapy might be recommended.  

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

Katherine Banwell:

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

Dr. Stein:

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

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

Katherine Banwell:

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

Dr. Stein:

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

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

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

Katherine Banwell:

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

Dr. Stein:

Yes, always call. Always call.  

Katherine Banwell:

Okay. I want to make sure we get to some of the audience questions. These were sent to us in advance of the program. Let’s start with this one from Patrick. He writes, “Are there any clinical trials looking at maintenance therapy for the AML patients, especially older patients?” 

Dr. Stein:

Yes, there are a number of clinical trials that are looking at maintenance therapy for older patients with acute myeloid leukemia. Some of those trials are maintenance therapies with targeted agents that are against specific mutations. Some of those trials are clinical trials with more broadly active agents that might be able to be used as maintenance therapy, so yes. Maintenance therapy is something that is really coming to the fore, and I would encourage you to seek out trials that might offer maintenance therapy.

Katherine Banwell:

Aaron sent in this question: “What are the most promising new effective drugs on the verge of being approved by the FDA, and what do they do?” 

Dr. Stein:

Yeah, so I’ll just mention the one I mentioned a second ago, and that’s the class of drugs called menin inhibitors. I wouldn’t quite say they’re on the verge of being approved by the FDA, but I think that they’re very, very powerful drugs that within the next two or three years, they will likely be approved by the FDA if the early clinical trials continue to pan out. And those are drugs that at least in the early experience, seem to be specific for patients with these NPM1 mutations or these MLL rearrangements. And your doctor will know what those are if you ask them, “Do I have an NPM1 mutation, or do I have an MLL rearrangement?” 

Katherine Banwell:

Thank you for that, Dr. Stein. And to our viewers, please continue to send in your questions to question@powerfulpatients.org, and we’ll work to get them answered on future programs.   

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

Dr. Stein:

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

Katherine Banwell:

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

Dr. Stein:

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

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

Katherine Banwell:

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

Dr. Stein:

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

Katherine Banwell:

That’s so positive. It’s great to hear that there’s been so much advancement and that there’s so much hope out there for AML patients. I want to thank you so much for taking the time to join us today, Dr. Stein.  

Dr. Stein:

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

Katherine Banwell:

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 powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us today.