Tag Archive for: AML treatment

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

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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A Look at Treatment Strategies for High-Risk AML Patients

A Look at Treatment Strategies for High-Risk AML Patients

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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What Does Triplet Therapy in AML Mean for the Future?

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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Why Is the Menin Pathway Important in AML?

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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What Does Triplet Therapy in AML Mean for the Future (2)

What Does Triplet Therapy in AML Mean for the Future?

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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The Importance of the FLT3 Mutation in AML

The Importance of the FLT3 Mutation In AML from Patient Empowerment Network on Vimeo.

What do acute myeloid leukemia (AML) patients need to  know about FLT3 mutation? Dr. Naval Daver from the University of Texas MD Anderson Cancer Center discusses considerations about the mutation. Learn about the incidence of the FLT3 mutation, risk of relapse, and treatment options.

[ACT]IVATION TIP from Dr. Daver: “ it is very important to know the status of the FLT3 the mutation, both in diagnosis to see if one would benefit by the addition of the FLT3 inhibitor to the frontline induction chemo as well as in relapse because this would open up the option for FLT3  inhibitor targeted therapies, which would probably have the best chance of response and long-term outcomes. 

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

Transcript: 

Art:

Dr. Daver, for AML with a FLT3 mutation, what have we learned, and what is currently being investigated?

Dr. Naval Daver:

AML with the FLT3 mutation is very important from both prognostic and from therapy perspective, prognostically, this is considered to be one of the high-risk mutations, it’s also one of the most frequent mutations in AML in, seen in about 30 to 35 percent of younger and about 15 to 20 percent of older patients with AML, and these patients often have very prolific disease, elevated white count leukocytosis. And without the addition of FLT3 inhibitors, there is a high risk of relapse and a short overall survival. 

Over the last 15 years, a number of targeted therapies called the FLT3 inhibitors have emerged, these started with the first-generation FLT3 inhibitors drugs, such as lestaurtinib and sorafenib (Nexavar), now we have the second-generation FLT3 inhibitors, this includes drugs like gilteritinib (Xospata), quizartinib, and crenolanib which are more potent, specific, and better tolerated.

The first study that showed that the incorporation of FLT3 inhibitors improves outcome was a study called RATIFY Study, this is a frontline study looking at newly diagnosed FLT3 mutated younger patients where we added the FLT3 inhibitor midostaurin (Rydapt or Tauritmo), which is the first-generation FLT3 inhibitor to the standard induction chemo versus a placebo, added to standard induction chemo, induction chemo being standard of care to that time and this showed that in the addition of FLT3 inhibitor to induction chemo did improve remission rates and overall survival as compared to induction, and led to the approval of the FLT3 inhibitor midostaurin in the frontline setting. 

Since then, two other FLT3 inhibitors, second-generation potent FLT3 inhibitors drugs called gilteritinib, and lestaurtinib have also been evaluated. Gilteritinib, in a relapsed setting where single-agent gilteritinib, has given 50 to 60 percent response rates and has been extremely well-tolerated and much better than any other salvage treatment in the FLT3 space that we have ever seen, and in the frontline setting quizartinib and second-generation inhibitor also very recently, just a few months ago, there was data showing the combination of his art with intensive chemotherapy improved survival as compared to intensive chemotherapy alone. 

And so we think we are…they will be a third for the inhibitor to get approved, so there’s been a lot of progress overall in the three space, and there are other newer FLT3 inhibitors also in early clinical investigation that we think could eventually be as part or even better, the activation point related to this question is that, for the inhibitors have dramatically improved outcomes, both in the frontline setting when added to traditional backbone intensive chemotherapy as well as potentially lower intensity therapy, as well as in the relapsed refractory setting, and it is very important to know the status of the FLT3 the mutation, both in diagnosis to see if one would benefit by the addition of the FLT3 inhibitor to the frontline induction chemo as well as in relapse because this would open up the option for FLT3  inhibitor targeted therapies, which would probably have the best chance of response and long-term outcomes. 

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What Different AML Subtypes Are More Prevalent in Certain Demographics?

What Different AML Subtypes Are More Prevalent in Certain Demographics? from Patient Empowerment Network on Vimeo.

Are some acute myeloid leukemia (AML) subtypes more common in some demographic groups? Dr. Naval Daver from the University of Texas MD Anderson Cancer Center discusses different forms of AML. Learn about the extent of knowledge about AML subtype demographics.

[ACT]IVATION TIP from Dr. Daver: “Patients, when they transformed what we call secondary AML or MDS, seemed to have a higher predilection for certain high-risk communications such as TP53, and these are best treated with ongoing frontline clinical trials at large academic centers.

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Transcript: 

Art:

Dr. Daver, what are the different subtypes of AML, are various subtypes more prevalent in certain demographics?

Dr. Naval Daver:

The main way we have classified AML has actually been changing, so when we talk about subtypes  there are actually two different classification systems like WHO and the ICC or ELM classification system. Traditionally, we have been using the ELM for prognostic classification of AML, this divides patients into three major buckets, what we call a favorable intermediate and adverse, and these are based on the underlying chromosome cytogenetics abnormalities and molecular or next-generation sequencing profile of the patients.

In general, in AML there has actually been limited data and publications regarding the demographic distribution, whether it’s regional or racial or cultural, one of the things that we do know, for example, in acute lymphoblastic leukemia is that in the Hispanic population, there seems to be higher frequency of things like FLT3-positive ALL. 

But in the AML population, there actually does not seem to be, at least based on published data, huge differences in the molecular or cytogenetic presentation. We have seen some data from different countries that there may be a difference in the prevalence of communications across different regions. For example, in Japan, we do see that the incidence of FLT3 and NPM1 appears to be lower than what has been reported in the United States.

Also, we see in Europe and United States, the incidence of these mutations with FLT3, NPM1 is similar, and then we are seeing in some of the larger academic centers in the U.S., there is an enrichment of referral of patients with TP53, which is very adverse and most difficult to treat mutation, and a lot of that we think is because patients with solid tumors and with other hematological malignancies are surviving longer with the CAR-T therapies, immunotherapies, and because it is over time, they have a risk of developing second AML, which is enriched for TP53 mutation, so we do see over the last two decades that from TP53, which used to be about 5 percent to 10 percent, is now up to 20 percent to 25 percent of AML and growing in proportion because it’s better survival and solid tumors and lymphomas.  

The activation tip related to this question is that in general, they don’t review discrepancies based on geography and race, and region in the molecular cytogenetics. However, we do see differences in patients who have received prior chemotherapy, radiation therapy, AML therapy for other solid tumors and lymphoma.

These patients, when they transformed what we call secondary AML or MDS, seemed to have a higher predilection for certain high-risk communications such as TP53, and these are best treated with ongoing frontline clinical trials at large academic centers. 

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AML Treatment Approaches Expand for Older and High-Risk Patients

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?

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?

Dr. Daver:

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 Can We Address Disparities in AML Among Diverse Populations?

How Can We Address Disparities in AML Among Diverse Populations? from Patient Empowerment Network on Vimeo.

What do acute myeloid leukemia (AML) patients need to know about care disparities? Dr. Catherine Lai from Penn Medicine discusses ethnic disparities and other factors. Learn about factors in AML care disparities and some available resources for patients to elevate their care.

[ACT]IVATION TIP from Dr. Lai: “Speak with your social worker, is there a resource that I can tap into that can help me with my care so that I can make sure that I can get the best access?”

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Transcript: 

Art:

Dr. Lai, how can we address disparities in AML among diverse populations?

Dr. Catherine Lai:

So this is an extremely important topic. And there was a large study that was recently published out of Chicago that looked at the different hospitals in the area and to look at ethnic disparities between white and Black populations and did find significant differences. Unfortunately, I would say that there are many factors that go into this, and a large portion of it is education and resources, and so what I would say is that we…we need to, as physicians and also the community, be better about educating our patients and being able to have access to resources so that everybody can get the same treatment.

And so involving other societies who support cancer to just get the word out that we need to…that we need to be aware of the differences so that we can address them specifically and make sure that for patients who don’t have resources that we are able to provide for them. So the activation tip here is that asking about resources, but we use a lot of Leukemia & Lymphoma Society grants that help our patients get access to and lower the cost of drugs, but also will…they will also provide grants just to help with cost of living, occasionally, there are other societies that can help with ride shares, and so I think even if you don’t know the specific…the specific society that can help, just asking to speak with your social worker, is there a resource that I can tap into that can help her help me with my care so that I can make sure that I can get the best access?

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Long-Term Effects Acute Myeloid Leukemia Patients Should Know

Long-Term Effects Acute Myeloid Leukemia Patients Should Know from Patient Empowerment Network on Vimeo.

What do acute myeloid leukemia (AML) need to know about potential long-term effects of treatment? Dr. Catherine Lai from Penn Medicine shares insight. Learn about medical considerations for monitoring and an activation tip to help patients ensure their optimal health for the long term.

[ACT]IVATION TIP from Dr. Lai: Make sure that you’re reporting all your symptoms, however small that they may be at your appointment, so it can be discussed in asking if it might be related to a late effect, and then also asking if there is a survivorship clinic or a program that you can be a part of.”

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Transcript: 

Art:

Dr. Lai, I was diagnosed with lots more than 20 years after my transplant, and there are the long-term effects that AML patients should be aware of. What are some of those effects?

Dr. Catherine Lai:

Yeah, so that’s an extremely important question and one that is often, often overlooked, unfortunately, even just from a time constraint perspective, but I would say it depends on the type of chemotherapy and the type of transplant, whether it was myeloablative you received radiation before your transplant, but, in general, I mean things to consider or just think about, it’s a big work, and so about your heart, your lungs, your thyroid, your kidneys, and also age-appropriate cancer screening as all things that need to be taken into consideration as late effects, if you are able to…if you’re able to find a cancer center with a survivorship clinic, I think that that’s an extremely valuable resource, because not only are they able to address these medical issues, but they’re also able to address the psychosocial component as well, and just overall general well-being.

And so I think just being aware of the fact that there are late effects and the activation tip being, is that to make sure that you’re reporting all your symptoms, however small that they may be at your appointment, so it can be discussed in asking if it might be related to a late effect, and then also asking if there is a survivorship clinic or a program that you can be a part of.  

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What Are Some Clinical Predictors for Relapse in Acute Myeloid Leukemia?

What Are Some Clinical Predictors for Relapse in Acute Myeloid Leukemia? from Patient Empowerment Network on Vimeo.

What do acute myeloid leukemia (AML) patients need to know about risk of relapse? Dr. Catherine Lai from Penn Medicine explains her perspective. Learn about relapse risk groups and testing that may help in determining risk of relapse. 

[ACT]IVATION TIP from Dr. Lai: Have a conversation with your provider about mutations, and do you as a patient have a specific mutation that can be…that can be tracked and also specifically what risk group on my end, what risk group am I in, because that also gives some insight as to your risk of relapse.”

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Transcript: 

Art:

Dr. Lai, what are some of the clinical predictors for relapse in AML patients?

Dr. Catherine Lai:

So, in general, predictors of relapse, some of it depends on what risk category you’re in, so whether or not you’re favorable, intermediate, or adverse risk of the adverse risk patients are more likely to relapse once in complete remission. The other thing, what I would say is that which mutations are present, a diagnosis is a good…also a good way to track and follow disease.

So if you have a specific mutation is to be able to follow that and to be able to quantify it on testing, and then be able to track to see if that increases over time as a predictor of relapse, I would say that, in general, minimal residual disease testing and these predictors or other blood-based markers are not standards.

So a lot of this is novel and is still not standard of care yet, so the activation to here is to just have a conversation with your provider about mutations, and do you as a patient have a specific mutation that can be…that can be tracked and also specifically what risk group on my end, what risk group am I in, because that also gives some insight as to your risk of relapse. 

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What Are the ASH 2022 Takeaways for AML Patients?

What Are the ASH 2022 Takeaways for AML Patients? from Patient Empowerment Network on Vimeo.

What do acute myeloid leukemia (AML) patients need to know about ASH 2022 updates? Dr. Catherine Lai from Penn Medicine discusses updates presented at the conference. Learn about combination treatments and a study that examined the use of chemotherapy before transplant. 

[ACT]IVATION TIP from Dr. Lai: “There are a lot of new, exciting therapies that are coming out, and that it’s really novel sequencing strategies and combinations that I think will be the future of AML.”

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Transcript: 

Art:

Dr. Lai, I had a transplant almost 30 years ago for relapsed AML and was not given intensive chemotherapy to get me into remission before the transplant. What are the takeaways from the ASH 2022 meeting? Is less more when treating AML?

Dr. Catherine Lai:

Sorry, that’s a great question, and what I just like to say that it’s so great that you are doing so well, so many years after, as you know, transplant is the original form of immunotherapy and is still the only potential cure for AML. And so with that being said, with at ASH what was seen was, I think a handful of things, so what I would say is that different combinations of drugs being used, so things looking at either at novel doubles and or triplets. Meaning combinations of two or three different drugs and how toxicity is affected, there are other also novel immunotherapies that are out there, not have been as groundbreaking as transplant, and I think that there is some way to harness the immune system to make treatment more effective, we just haven’t found that. Right, chemotherapy.

And then specifically, there was a large study, a large European study that was presented as the plenary session at ASH that talked about the role of chemotherapy before transplant. And what I would say, just speaking in general, is that the new immune system that a patient gets when they get a transplant takes…the new immune system, when a patient gets a transplant, it takes some time to take over, and that new immune system is able to fight off the leukemia, and so if a patient has a slow-growing leukemia, they might not need as much chemotherapy before the transplant, because the rate at which the leukemia will grow and won’t overburden the body before the new immune system takes over.

So I think that study was very provocative and gave some insight, but I still don’t think we have the complete right answer as to what chemotherapy should be used before transplant, I think that’s really tailored to each individual patient.

And then whether or not patients need chemotherapy after transplant also depends on disease burden and status, and taking into account measurable residual disease as well. So I would say the activation tip from the ASH 2022 meeting was that there are a lot of new, exciting therapies that are coming out, and that it’s really novel sequencing strategies and combinations that I think will be the future of AML.

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What Does Transfusion Burden Mean in Acute Myeloid Leukemia?

What Does Transfusion Burden Mean in Acute Myeloid Leukemia? from Patient Empowerment Network on Vimeo.

What do acute myeloid leukemia (AML) patients need to know about transfusion burden? Dr. Catherine Lai from Penn Medicine explains transfusion burden for AML patients. Learn about the range of transfusion burden and advice from an expert. 

[ACT]IVATION TIP from Dr. Lai: “Discuss how frequently transfusions are needed and how long you may be able to go without needing a blood or platelet transfusion with your physician.

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Transcript: 

Art:

Dr. Lai, what does transfusion burden mean in AML?

Dr. Catherine Lai:

Yeah, so transfusion burden is the amount of either patients’ blood that you have to receive and or platelets that you have to receive.

So when we say that somebody is transfusion-dependent, that means that they on their weekly blood checks or having to receive transfusions multiple times, whether it be twice a week or once a week, but somebody who cannot make enough blood and our platelets on their own to stay within a safe range and that they need to receive transfusions. 

Typically. now, this is again specific for an individual patient, but in general, most centers use parameters such as the hemoglobin less than 7, in which they get transfused red blood cells and a platelet count less than 10,000 for platelet counts, assuming that patients are feeling well and are healthy and they’re not bleeding.

So here the activation tip would be to discuss how frequently transfusions are needed and how long you may be able to go without needing a blood or platelet transfusion with your physician.  

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