AML Research Updates: News from ASH 2020

AML expert Dr. Jeffrey Lancet shares news from the 2020 American Society of Hematology (ASH) annual meeting. Dr. Lancet sheds light on headlines from the meeting including FLT3 inhibitor research, combination therapies with venetoclax, a promising inhibitor therapy, and shares his optimism about the future of AML treatment.

About the Guest:
Dr. Jeffrey Lancet is Chair and Program Lead in the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, FL. He is nationally and internationally recognized for his clinical research in the field of acute leukemias. Learn more about Dr. Lancet, here.

See More From INSIST! AML


Transcript

Katherine:

Hello and welcome, I’m Katherine Banwell. Today we’ll discuss the latest news from ASH 2020 and how AML patients can advocate for personalized care. Joining me is Dr. Jeffrey Lancet. Welcome, would you please introduce yourself?

Dr. Lancet:

Hi, sure. My name is Dr. Jeff Lancet. I’m at the Moffitt Cancer Center in Tampa, Florida where I am the Chair of the Malignant Hematology Department. We spend a lot of time treating patients and conducting clinical trials of Acute Myeloid Leukemia.

Katherine:

Dr. Lancet, the American Society of Hematology annual meeting just closed. What are the AML headlines from this year’s meeting?

Dr. Lancet:

Yeah, so as usual AML was a very busy area for clinical presentations this year at the ASH meeting focusing largely on novel and targeted therapies. I don’t believe that there were many practice changing delevelopments, per se, but rather discussions about many promising therapeutic strategies that are still under development and moving forward rapidly largely in the areas of targeted therapy, low intensity therapy, measurable residual disease, and things of that nature.

Katherine:

What does this research news mean for patients?

Dr. Lancet:

Well, I think that there is a lot to be encouraged about and maybe I’ll take the time to review some of the highlights in what was presented with respect to some of the novel therapeutic approaches that many of our patients can look forward to receiving in the not-too-distant future.

So we often talk about targeted therapy instead of, of course, one of the major targets over the years has been that of a mutated FLT3, which is one of the most common mutations in AML.

And at this meeting, we saw several presentations on clinical trials results utilizing Inhibitors of FLT3 with some emphasis on the most recently approved 2nd generation drug called gilteritinib.

There were, I thought, three major presentations focusing on gilteritinib. One was an update on a randomized phase 3 trial comparing gilteritinib plus azacitidine versus azacitidine alone in newly diagnosed unfit for induction chemotherapy patients with FLT3 mutations. Preliminary showing good tolerability and high composite complete response rates in the combination arm. 

There was another trial of gilteritinib plus venetoclax in relapsed refractory FLT3 mutated AML and what was interesting was that a very high percentage of patients achieved response with this combination of gilteritinib plus venetoclax. Many of whom were heavily pre-treated previously and many of whom had also got prior FLT3 inhibitor therapy during an earlier stage of the disease, so the combination of gilteritinib plus venetoclax in this more refractory setting was encouraging to see these promising responses.

And then we say some data reporting the effects of gilteritinib in combination with more traditional chemotherapy induction with a couple of studies demonstrating both high complete response rates, as well as high rates of mutation clearance of the FLT3 mutation. So those are very encouraging data that were presented with respect to the FLT3 mutated AML population. 

So another very important drug that reached the marketplace for AML recently is a drug called venetoclax, which is an inhibitor of a protein called BCL2. And this drug was recently FDA approved for use in combination with low-intensity chemotherapy drugs such as azacitidine or decitabine. And it seems as though the combination of venetoclax plus one of these hypomethylating agent drugs, azacitidine or decitabine, has resulted in very strong efficacy signals as recently published in the New England Journal of Medicine paper that reported on the results of the Phase 3 trial of venetoclax plus azacitidine.

So that has now become standard of care for older, less fit adults with newly diagnosed AML. The combination of venetoclax plus hypomethylating agent such as azacitidine. And naturally there’s been interest in really kind of taking it several steps further to advance the role of these combinations and to also look at additional drugs in combination with venetoclax plus hypomethylating agent therapy. So, we saw some of that at the ASH meeting this year.

One approach would be to take venetoclax and then to combine it with more intensive chemotherapy for perhaps more fit patients or younger patients that could undergo a more intensive program. So we saw presentations of venetoclax being combined with a drug called CPX-351 which is a novel liposomal formulation of two common chemotherapy drugs that had been approved a few years ago for secondary AML. And we also saw a combination strategy with venetoclax and a regimen known as FLAG-IDA, which is a commonly used induction regimen in Acute Myeloid Leukemia.

I think it’s important to recognize that although these trials they combine venetoclax with more intensive chemotherapy show signs of good efficacy with good response rates, there are definitely signals of increased toxicity, hematologic toxicity, primarily. Which is not really unexpected with venetoclax knowing that it can cause significant lowering of white blood cells, platelets, and hemoglobin.

Then finally, there is a lot of interest in doing these types of combinations with venetoclax in different subsets of AML. And one subset of AML that has been very important recently is that of the IDH-mutated AML population of patients. IDH is a fairly common mutation that occurs in either in the form of IDH1 or IDH2, and there’s about a 15-20% incidence of IDH mutations in AML. Though we do have an inhibitor for both of these types of mutations, ivosidenib for IDH1 and enasidenib for IDH2, but there also appears to be a strong role for venetoclax plus azacitidine in IDH mutated AML. We saw from a series of patients presented by a physician at MD Anderson looking at outcomes with venetoclax plus azacitidine in IDH mutated AML. The response rates were very high when you give HMA plus venetoclax to these patients with IDH mutated AML. But, I think more importantly, is that there were what we call high intra-patient response rates when switching between venetoclax and HMA therapy with IDH inhibitor continued regimen. In other words, a patient would have a good chance of responding to the initial therapy, then, if or when that therapy stops working, having a good effect from the salvage therapy with the other regiment, So if you received initially azacitidine plus venetoclax, and then had a relapse, the IDH inhibitors worked well and vice-versa if have received an IDH inhibitor, then subsequently received HMA/venetoclax at a later time point, that also worked well.

So it’s encouraging to see that you can potentially sequence these drugs and get continued responses along the way that ultimately we think that will help survival and keep patients in a better state of health for longer.

So I just wanted to take a few minutes also and discuss some of the newer more novel therapies that are really hitting or approaching the landscape right now. One of these is called CC-486, also known as oral azacitidine or onureg, and this drug was shown in a recent literature to prolong overall survival in patients who are in first remission from their AML who had received induction chemotherapy. So this drug was used as maintenance therapy after a variable number of consolidation regimens and people who got this onureg or azacitidine drug as maintenance therapy, it resulted in longer survival compared to those who had received placebo. This was presented at last year’s ASH meeting, but this year’s ASH meeting provided an update, a very important update, showing that the overall survival advantage from this drug, this oral azacitidine drug, when used as maintenance was independent of whether a patient had measurable residual disease at the time that they went on to the maintenance therapy. In other words, whether you had MRD (measurable residual disease) or not at the time of the study entry, your responses were still more favorable, your outcomes were more favorable if you received this oral azacitidine drug. So this was FDA approved earlier this year for patients in the maintenance phase of therapy for AML who had got prior induction chemotherapy. 

And importantly, this drug was also shown to be able to convert about 25% of patients who were positive for measurable residual disease, to convert them from positive to negative. So even though they were in remission, they had measurable residual disease and this drug in about 25% of the cases converted them from positive to negative. So that’s a very important finding as well. 

Another important drug that I think you should keep your eye on is a drug called magrolimab. This is an antibody against a certain type of protein that is present on an immune system cell called the macrophage. And when this magrolimab drug is combined with azacitidine in a recent clinical trial, it was demonstrated very high response rates of over 65%, and in particular in patients with P53 mutation, which is a very bad mutation to have in most cancers including AML. In patients with this high-risk mutation, the combination magrolimab with azacitidine appears to be effective based on the early data that we have with high response rates.

And then finally, I just wanted to make mention of another important area in, not really just AML, but all cancer, and that’s outcomes disparities between different races and ethnic groups. And we saw a very important presentation at the plenary session this year where the authors reported outcomes amongst younger patients with AML who are African American compared with caucasion. And the data clearly indicated a worse overall survival amongst black patients compared to white patients under age 60. And this included patients who are enrolled in clinical trials. So that, it appeared that African American patients had a worse outcome than Causian patients with Acute Myeloid Leukemia. Highlighting the need to better understand various risk factors and other factors that play into these disparate outcomes between our black American population and our white American population, which I think could shed light on additional disease characteristics that many help everybody.

Katherine:

Dr. Lancet, thanks so much for joining us today

Dr. Lancet:

Thank you very much for having me. It was good to be with you.

Katherine:

And thank you to our audience, I’m Katherine Banwell.


Don’t miss an episode and subscribe to PEN’s Empowered! Podcast wherever podcasts are available.

Expert Advice: How Can AML Testing Inform Your Treatment Choices?

What tests should follow an AML diagnosis and why? Dr. Hetty Carraway, an AML specialist from Cleveland Clinic, outlines key testing for patients with AML, how the results impact treatment choices, and provides advice on advocating for yourself, stressing the importance of including a caregiver as part of the conversation.

Dr. Hetty Carraway is Director of the Leukemia Program at Cleveland Clinic. Dr. Carraway cares for patients with acute leukemia and bone marrow failure states. Learn more about Dr. Carraway, here: https://my.clevelandclinic.org/staff/18591-hetty-carraway


Transcript:

Katherine:    

Welcome to Empowered, a podcast by the Patient Empowerment Network. I’m your host, Katherine Banwell.

Today we’ll discuss how you can be proactive by insisting on better AML care and personalized treatment options. Joining me is Dr. Hetty Carraway.  Welcome. Would you please introduce yourself?

Dr. Carraway:   

Hi. My name is Dr. Hetty Carraway. I’m one of the physicians at the Cleveland Clinic. I work as the Director of the Leukemia Program, and I spend most of my time caring for patients with acute leukemia and bone marrow failure states.

Katherine:    

Thank you. Let’s start with the basics. What essential testing should AML patients undergo following a diagnosis?

Dr. Carraway:  

This is a pretty standard workup for patients that have this diagnosis of acute leukemia.

For most of our patients we always evaluate with a peripheral blood count including a complete blood count with differential, typically a comprehensive metabolic panel, and looking at a test called a uric acid, which looks at the cell turnover and the cellular debris in terms of the burden on the kidney. We often will get a bone marrow biopsy with aspirate for patients, and in the diagnosis of leukemia typically that’s already been done.

There are tests that are sent off of that aspirate called a test for chromosomes, whether it’s comprehensive cytogenetics or FISH, for fluorescence in situ hybridization. We’re often testing using a study called NGS or next generation sequencing looking for specific mutations of genes known to be important in the pathogenesis of leukemia.

Furthermore, we often get a test called flow cytometry from that aspirate looking at the markers on top of the leukemia cells that help us to identify the blast population. So, I would say those by and large are the tests in the bone marrow biopsy that we get, which are innumerable and detailed.

They often take some time to get back, so at the time of the diagnosis patients know that they have a diagnosis of leukemia, but those additional chromosome tests or mutation testing that can take up to two weeks if not longer to get back. And so, it’s important to follow up on that information later on and say, has that testing come back? If so, how does that change any of what the decisions are moving forward?

Katherine:  

Genetic testing can often be confused with molecular testing. What’s the difference between the two, and why should patients undergo the testing?

Dr. Carraway:           

The chromosome testing and the mutational testing help us to really classify the risk in terms of the leukemia itself, whether or not that leukemia is responsive to chemotherapy alone, or if it means that there’s a higher likelihood of that leukemia not being controlled with leukemia only.

In that setting, we often then move towards transplant for curative intent in addition to the chemotherapy. The reasons to get the information is to really help us better tailor the therapy for each individual patient. That information really does help us guide not only the upfront therapy for some patients but even the long-term therapy. It can be incredibly overwhelming to have too much information at the get-go, so in some senses it’s better to have these pieces as they unfold over time.

For other patients, they want to know what exactly the plan is going to be A to Z from day one. That is of course more challenging now that it just takes time to get this information. I think what they need to know is that we’re working hard to get that information.

As soon as we get it, we don’t hold back. We reveal and share that information and come together to say, this is what this data or information means, and these are some of the choices that we either recommend that you consider, and these are the risks and benefits to those considerations.

Katherine:    

Let’s look at something that is similar to what you’ve just been talking about. How do test results impact treatment and overall care?

Dr. Carraway:   

When you asked me how come chromosome or genetic information is different than mutational information, the chromosomes can help us to figure out where patients land in terms of prognosis. That information is different than the mutational testing. Both of those pieces can help us figure that out.

The mutational test, I will tell you, does help us figure out are there targets on the leukemia that allow us to use therapy that’s directed to that mutation. The key example I’ll give is a mutation in a gene called FLT3. That particular mutation has an agent now that is F.D.A. approved called Midostaurin, and so once we know that a leukemia harbors a FLT3 mutation we often add a drug called Midostaurin to the backbone therapy that is used for patients.

Now, that’s important, and now there are more and more genes that when mutated we have novel therapies that direct against that specific tag that’s on the leukemia and helps to improve eradication of the disease or control of the disease if you will.

That’s different than the genetic information when we’re looking at chromosomal changes that may allow us to say in the rare instances of  favorable cytogenetics like a translocation of chromosome 15 and 17 consistent with ATL, the treatment for that type of leukemia,  acute promyelocytic leukemia, is very different than what we do for the majority of other leukemias. The prognosis for that leukemia is also very different. It helps to tailor the regimens, and it helps to select specific therapy that may be helpful to each individual patient.

Katherine:    

Dr. Carraway, you just mentioned FLT3. Would you tell us about the common mutations in AML and how these may impact treatment options?

Dr. Carraway:   

There’s a multitude of mutations that we’re now following in patients. The way that we follow them is by doing this next generation sequencing test at the upfront time at diagnosis.

The reason why we’re doing that is because those mutations can regress with therapy, or they can progress where you gain additional mutations that happen as the disease progresses. Even if it’s responding to therapy or as it loses response to therapy and reemerges, it may reemerge with different mutations. As a result of that, it may change what therapy we select. Our ability at this point in being to recommend exactly at what time points we are checking the next generation sequencing we’re still learning right now as to what are the key times to do that testing.

In general, most institutions are doing that next generation sequencing at the time of diagnosis, and then also for some patients before they go to bone marrow transplant and even after bone marrow transplant.

For some of those patients that unfortunately relapse, we’re also making sure to retest the next generation sequencing mutation testing to see are there new mutations that have come about that weren’t there before?

Katherine:   

I understand there’s something called IDH.

Dr. Carraway:   

You were also asking about what other mutations besides FLT3 happen in patients with AML. FLT3 is one such mutation. NPM1 is another mutation that often it frequents patients that have AML. Those two mutations happen in about 30 percent of patients with AML. There are other mutations such as DNMT3A, ASXL1, and TET2 that we typically see in patients with MDS or even a pre-leukemia state called CHIP. For other patients, we have mutations that are targetable like IDH1 or IDH2.

Those two mutations happen in probably 10 percent to 15 percent of patients diagnosed with AML. Why are those important? They’re important because we have oral medications that are pills that patients can take. In the relapse setting for many patients after induction or intensive chemotherapy, they can use these oral therapies to try and control their leukemia. These are pretty exciting.

All of these oral therapies have been approved in the last two to three years in the space of leukemia, so it’s been a game-changer in terms of identifying these mutations and then identifying drugs that target those mutations. It’s really changed the landscape for patients with AML. It’s new information, and that’s why as patients you want to hear about this so you know what questions to ask and you know, can you tell me, am I a candidate for one of these oral medications that is now available for patients with AML?

Katherine:   

What advice do you have for patients when it comes to asking for appropriate testing and speaking up in their own care?

Dr. Carraway:   

This is so important. I think patients are leery to stir the pot or be difficult. I think coming from a place of inquiry, teach me about this, that, or the other thing, help me understand this, that, or the other thing – I would like you to show me why this decision or talk with me about why this decision versus another decision might be better for me compared to somebody else.

I can’t underscore the importance of advocating for yourself and asking questions about why am I getting this drug? What are the side effects to this drug? What is my prognosis? What is different about my case versus somebody else’s situation? How do I best prepare myself in getting ready for the therapy that I’m about to go through?

Those are all important questions that patients should ask. They should certainly have people, if possible in their family be advocates for them. I welcome that, and I think that that’s a really important part of going through this type of therapy for any patient. Your physician should welcome having your involvement in that. Don’t be shy about that. It’s your health, and any investment in that the most important people in that is inclusive of you and your caregivers. They should be a welcome part of the team.

Katherine:    

Dr. Carraway, thanks so much for joining us today.

Dr. Carraway:    

Thank you for the opportunity to be here.

Katherine:     

And thank you to our listeners for joining us for Empowered. Visit PowerfulPatients.org to access resources to help you be a proactive patient in your care decisions. I’m Katherine Banwell.


Don’t miss an episode and subscribe to PEN’s Empowered! Podcast wherever podcasts are available.

Empowered! Podcast: Meet Andrea Conners

Today, we’re extremely proud to introduce our first-ever Empowered! podcast. Empowered! will bring you conversations around topics that are important to patients and care partners.

For our first episode, we meet Andrea Conners. Andrea is Patient Empowerment Network’s Executive Director. Andrea shares a little bit about herself, about PEN, and her inspiration in getting involved.

 


What You Should Know About Acute Myeloid Leukemia (AML)

This podcast was originally published on City of Hope Radio by Guido Marcucci, MD, here.

 

Topic Info: Acute myeloid leukemia (AML) is characterized by rapidly-developing cancer in the myeloid line of blood cells, which is responsible for producing red blood cells, platelets and several types of white blood cells called granulocytes.

Because AML grows rapidly, it can quickly crowd out normal blood cells, leading to anemia, susceptibility to infections and uncontrolled bleeding.

Due to the aggressive nature of AML, this disease usually requires intensive treatment, which may include chemotherapy, radiation therapy, immunotherapy, and stem cell transplantation.

The following represent symptoms typical for AML:

  • Fever with or without an infection
  • Frequent bruising or bleeds that do not clot
  • Leukemia cutis (multiple lesions with a firm or rubbery consistency that may be pink, red, red-brown or blue-violet in color)
  • Night sweats
  • Pain in the bones or joints
  • Pain or feeling of fullness below the ribs
  • Petechiae (flat, pinpoint spots under the skin caused by bleeding)
  • Shortness of breath
  • Weakness or feeling tired

Listen in as Guido Marcucci, MD discusses AML, its symptoms, diagnoses, and treatments.

Acute Myeloid Leukemia: Diagnosis & Prognosis

This podcast was originally published on The Bloodline With LLS on April 22, 2019, here.

 

Join Alicia and Lizette as they speak with Dr. Martha Arellano, Associate Professor of Hematology and Oncology and Program Director of the Hematology and Medical Oncology Fellowship Program at the Winship Cancer Institute of Emory University in Atlanta, Georgia. On this episode, Dr. Arellano defines acute myeloid leukemia (AML) and how it is diagnosed. She addresses questions about cause and prevention and how treatment is determined for younger vs older patients. Dr. Arellano also explains the importance of a patient getting a second opinion to not only increase their education about diagnosis and treatment options but also as a way to move forward with a team they trust.

Early Detection of Acute Myeloid Leukemia (AML)

This podcast was originally published by Cancer Cast (Weill Cornell) here.


 

Pinkal Desai, MD – Speaker Bio

How specific gene mutations can enable prediction of acute myeloid leukemia (AML) up to a decade prior to disease development.

Guest: Pinkal Desai, MD, hematologist and medical oncologist at the Weill Cornell Medicine and NewYork-Presbyterian Hospital Leukemia Program.

Host: John Leonard, MD, world-renowned hematologist and medical oncologist at Weill Cornell Medicine and NewYork-Presbyterian Hospital.

Why Getting a 2nd and 3rd Opinion Made a Difference In Her Cancer Treatment, With Sasha Denisova

This podcast was originally publish on WE Have Cancer by  on May 7, 2019 here.


Sasha Denisova – WE Have Cancer

Seeking out a 2nd and 3rd opinion in her cancer treatment resulted in a dramatic improvement in Sasha Denisova’s quality of life.

Sasha first appeared on this podcast in Episode 83 where she shared the struggle she faced getting doctors to take her colorectal cancer symptoms seriously.

During our latest conversation she discussed why she made the decision to forego treatment at the Mayo Clinic in Minnesota to seek treatment at Memorial Sloan Kettering in New York City. We also discussed:

  • How she got the courage to challenge the initial treatment recommendations made by her doctor and why it’s important for everyone to advocate for their best care.
  • The importance 0f seeking out opinions from the top rated cancer facilities in the U.S.
  • How she eased herself back into working out in the gym and why working with a guided fitness instructor was important.
  • Why exercise is vital to her well-being and how most cancer patients can find an exercise routine that works for them.

Take Control Of Your Care When You’re Seriously Sick via NPR

This podcast was originally publish on NPR by John Henning Schumann, Mara Gordon, and Chloee Weiner on September 7, 2019 here.


Finding out you have a serious medical condition can leave you reeling. These strategies from medical and lay experts will help you be in control as you navigate our complex health care system and get the best possible care.

Here’s what to remember:

1. Your primary care doctor is the captain of your health care team.

With any serious diagnosis, there will usually be more specialists to see. Having a primary care doctor you trust helps coordinate the information flow and keep track of the big picture. Your primary is on her toes for possible medication interactions. Regular preventive measures shouldn’t be overlooked, either.

2. Don’t be afraid to get a second opinion.

If you’re offered treatment such as chemotherapy or surgery that can be life-altering, it’s crucial to get more than one opinion, ideally from a doctor working for a different institution. Oncologists and surgeons expect patients to seek second opinions — many provide them as a major part of their practice. If your doctor resents you seeking more opinions, that’s a red flag.

3. Get organized, stay organized, and find someone to help you if you can’t do it yourself.

Make a list of what you hope to accomplish at the doctor’s office. If for some reason you aren’t able to take notes, bring someone along who can act as an advocate and make sure your concerns aren’t overlooked. Ask for copies of your medical chart and test results so that you are part of the conversation — you have a legal right to see your records.

4. If you need a procedure, go to someone who does it all the time.

It’s true for medical care as it is in life: The more a doctor does a procedure, the better at it she’ll be. This means fewer complications and better outcomes. It’s OK to ask your doctor how many times she’s done a procedure; a high volume means competence when things go as planned, and calmness for unforeseen complications.

5. Use the Internet, but use it wisely.

Contrary to what you may think, your doctor wants you to be well-informed and engaged with your health. There’s more medical information available online than ever before, but a lot of it is garbage. Stick with trusted sources like the National Library of MedicinePubMed.gov, or learn about and use the U.S. Preventive Services Task Force.

6. Figure out what matters to you, and fight for it

Our default setting for health care is that more testing is always good. But that’s often not the case, as tests have side effects and can cause undue anxiety because of false positives or incidental findings. Have a frank conversation with your doctor about your values and what you want (and don’t want!) and you’ll be an empowered patient with a doctor as your advocate, not your adversary.

Learning How to Simplify Cancer With Joe Bakhmoutski

This podcast was originally publish on WE Have Cancer by Lee Silverstein on June 18, 2019 here.

Joe Bakhmoutski – WE Have Cancer

Joe Bakhmoutski was diagnosed with Testicular cancer in 2016.He founded Simplify Cancer  to provide support and advice to those touched by cancer. During our conversation we discussed:

  • Why he created Simplify Cancer
  • How he came to be diagnosed with Testicular cancer
  • How people perceive various cancers and how some are deemed “embarrassing”
  • What patients can do to prepare for their first oncologist appointment and the free tool he offers on his website to assist with this.
  • The book he’s writing to help men dealing with cancer.

Links Mentioned in the Show

Simplify Cancer – http://simplifycancer.com/