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Improving Response and Expanding AML Treatment Options

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Published on December 20, 2019

For acute myeloid leukemia treatment, what news stands out from the 2019 American Society of Hematology (ASH) Annual Meeting for patients? A panel of renowned experts including Dr. Eunice Wang, Dr. Amer Zeidan, Dr. Uma Borate and Dr. Hetty Carraway discuss exciting research developments in AML and how it translates to the clinic. The experts provide an overview of recent FDA approvals, updates on oral agents and immunotherapies and explain how treatment plans are being tailored to specific patient populations. 

This is a Patient Power program. We thank AbbVie, Inc. and Genentech, Inc. for their support. These organizations have no editorial control, and Patient Power is solely responsible for program content.

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Transcript | Improving Response and Expanding AML Treatment Options

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Andrew Schorr:         

Hello, and welcome to Patient Power. I’m Andrew Schorr. We’re on location in Orlando, Florida. Why are we here? Because across the street at the big convention center, we’ve had more than 25,000 people who study blood-related conditions and treat it, and of course, fortunately now in recent years, we’ve had a lot more to talk about in acute myeloid l eukemia. It offers great hope to people who are affected by this acute condition.

Joining me now are four leading experts, and we’re here to discuss this, and also in a little bit we’ll be joined by a patient who’s been treated successfully for AML, and that’s the good news. All right? So, let me introduce our guests. I’m going to let them introduce themselves as well, but first, let’s go way down to the end. Dr. Uma Borate, from Oregon Health and Science University in Portland, Oregon. What’s your title there? What’s your area of study?

Dr. Borate:                 

So, I work at the Oregon Health and Science University. I’m an assistant professor, in our Section for Hematologic Malignancies, and I mostly study the blood cancers known as myelodysplastic syndrome and acute myeloid leukemia, or AML.

Andrew Schorr:         

Okay, and you’ve been on Patient Power before. Welcome back.

Dr. Borate:                 

Thank you.

Andrew Schorr:         

Okay, let’s go to Buffalo, Dr. Eunice Wang.

Dr. Wang:                  

Hi, I’m Dr. Eunice Wang. I’m the Chief of the Leukemia Service at Roswell Park Comprehensive Cancer Center. We run a very active clinical service and clinical file portfolio focusing on early phase clinical trials, those drugs that are very, very early in development. I also run a transitional research lab, where we are doing experiments in cells in mice to come up with the next best thing to treat AML patients.

Andrew Schorr:         

Okay, great. All right, we’re working down the East Coast, we’ve made it to New Haven, Connecticut, Yale University, Dr. Amer Zeidan.

Dr. Zeidan:                 

Correct.

Andrew Schorr:         

Right, and what’s your area there?

Dr. Zeidan:                 

Yes, I’m an associate professor of medicine at Yale University. I also focus on myeloid malignancies, especially patients with myelodysplastic syndromes, as well as older patients with acute myeloid leukemia. So, I also do clinical trials focusing on targeted agents as well as immune therapies for those patients. I also do a lot of large database and outcomes research, which I think is very important compliment to understand—not only how these therapies work in the real-life setting, which is most important on the patient level, but also how we can learn from that and try to improve the outcomes, what they are.

Andrew Schorr:         

What’s the impact? 

Dr. Zeidan:                 

Correct.

Andrew Schorr:         

Yeah, yeah, okay, and now let’s go to Cleveland. Dr. Hetty Carraway from the Cleveland Clinic, and Hetty, what’s your area there?

Dr. Carraway:            

I currently am an associate professor in the hematologic malignancy program at the Cleveland Clinic. I also serve as the vice chair of strategy and enterprise development at the cancer institute as well. I spend most of my time taking care of myeloid malignancy patients, MDS, AML and other leukemias as well. 

Andrew Schorr:         

Okay, let’s start with you right here. So, what’s the buzz about AML? You have so much that you’ve been able to talk about in the last couple of years, and I’m going to ask all of you, and you can sort of be added in, but what’s impressed you?

Dr. Carraway:            

Well, the landscape of AML is really changed in the last two years. We now have drugs that are approved, that we never really had the ability to use combinations, that we now can test and use for patients. I would say in the last two years we’ve had about seven or eight novel drugs that have been FDA-approved for patients with AML, and in the last 30 to 40 years that hadn’t happened, so it’s a very exciting time to be in this arena, not only because of the drugs, but because of the testing that we’re doing, looking at specific mutations, that are on the leukemia, that help us focus the chosen therapies that may best fit a patient.

Andrew Schorr:         

So, AML is not a one size fits all? 

Dr. Carraway:            

Currently, no. We’re learning that there may be populations of patients that may benefit more from one targeted therapy, for example, than another. So, it’s a very heterogeneous disease, and I think our discussion today will probably highlight a lot of that.

Andrew Schorr:         

Let’s get to that, Dr. Zeidan. So, if people are different, then you have to do testing now, and testing has improved as well, so a patient comes to you, you can get a clearer picture of what version of AML you’re dealing with. That testing is critical, isn’t it?

Dr. Zeidan:                 

Correct, yes, so the testing is very important on two levels. The first one is to actually confirm what the patient has, whether they actually have acute myeloid leukemia. In certain situation, the diagnosis itself can be challenging, and some patients are diagnosed with what we call higher risk MDS, and some patients are diagnosed with acute myeloid leukemia. Sometimes, the definition of where the cutoff between the number of the blasts, the number of the cancer cells in the bone marrow determines that. The second level is to try to pick up the best treatment, and also understand the prognostic outcome, like how well, or poorly is the patient likely to do, based on the genetic studies that we have for them? So, testing for those mutations is becoming extremely important, and becoming, really, a part of the standard of care that I think every patient with acute myeloid leukemia should really have. 

Andrew Schorr:         

Right. I just want to interject. We’ve been interviewing a lot of AML experts, and so, it’s an acute condition for you or your loved one. You need to make sure, wherever you are, that your situation is clearly understood, specifically with testing. Is the diagnosis correct, of course, which illness? You talked about which version of AML. Have the right tests been done? If you’re not near one of these major centers, maybe you and your doctor make a call, or you get to one of these centers, so that, with this changing landscape we’re going to talk about, is brought to bear in your case. Okay, so, Dr. Wang, things that have impressed you here, news, you have poster sessions, presentations and all that. What is standing out now? 

Dr. Wang:                  

There are a lot of exciting new therapies and lot of exciting new approaches that are in development. Some of the most exciting news that I’ve seen is the development of an oral drug, that can actually be used for what we call maintenance therapy. So, patients that are getting up-front intensive chemotherapy, often times when they finish their therapy, we just stop, and unfortunately, up to half of those patients could relapse, and now there is an oral version of a drug called azacitidine (Vidaza), which has been shown, if you take it for a couple weeks out of every month, that it can dramatically prolong survival and prevent the disease from coming back, so it’s… 

Andrew Schorr:         

That’s not a new drug.

Dr. Wang:                  

…no, it’s a new formulation. It’s an oral formation of a drug that we typically use for combination of up-front therapy for myelodysplastic syndrome, and AML, and this new pill version, convenience-wise, adherence-wise, compliance-wise is offering a way to, on a day-to-day basis, provincially delay, or prevent the disease from recurring. So, I think that is a major development, and I think we’re going to see more of that drug. I think we’re moving further and further into oral chemotherapy for our disease, away from that high, intensive chemotherapy that requires people to be in the hospital for weeks and weeks and weeks.

Andrew Schorr:         

One of the drugs I’ve heard about, also another oral. I have chronic lymphocytic leukemia, so they came out with this drug, venetoclax (Venclexta), that’s used in AML as well, sometimes in combination with others.

Dr. Wang:                  

Yes, so, venetoclax has astonishingly now also become a standard of care therapy for acute leukemias, based on some of the data and the safety profile from individuals like yourself, who have taken it for chronic leukemia. It has improved the results of azacitidine for acute myeloid leukemia patients. We’re now seeing about two-thirds of patients with newly diagnosed acute myeloid leukemia, particularly older individuals, 70s, 80s, patients that don’t want to get intensive chemotherapy, be able to take a pill and a shot chemotherapy together and have a response rate of 60 percent to 70 percent. That’s a game changer for us, and that type of chemotherapy can be continued in the outpatient setting. So, that sort of changed the way we think about it. Now, we used to think high-dose chemotherapy, put you in the hospital, nausea, vomiting, low blood counts, and now we’re moving towards being able to treat older individuals safely in their own homes.

Andrew Schorr:         

Dr. Borate, you’ve been nodding your head. So, typically people with AML are older, typically. So, here, having these oral therapies then, as Dr. Wang was saying, it’s a game-changer as people can live a more normal life.

Dr. Borate:                 

That’s correct, and just to elaborate a little bit of what’s already been mentioned, as Dr. Zeidan said, the first step is really testing and figuring out if you have AML, but also, what are the different genetic changes, also known as mutations, that are present in your AML? Based on the type of mutations that are present in your AML, we have different therapies that can target those mutations. Majority of them are now oral therapies, so a common mutation is an IDH1, so a lot of letters and numbers, or IDH2, and now we have two approved oral agents that you can actually give patients that they can take in their own homes. And just as you mentioned combining this drug called azacitidine with another oral agent called venetoclax. We could combine, and there’s data presented at this meeting of combining these different oral agents that are targeted for IDH1 and IDH2 mutations, that is azacitidine. that can then even improve on the response that we’re seeing in AML patients that have these particular mutations.

Andrew Schorr:         

Okay, so, Dr. Carraway, so let’s say you try one of these combinations or a certain drug. If you’re measuring and you’re seeing, you’re not getting the response you want, do you have another horse to ride? Do you have another choice?

Dr. Carraway:            

That’s a great question. I think I always go back to, “Are we really convinced that we’ve failed the first therapy?” These therapies, we want them to work quickly, and I think one of the first principles is that they don’t often work quickly alone. So, we talked a little bit in the up-front setting that you can use some of these agents even in the relapsed setting, we’re able to use some of these targeted agents as well. So, venetoclax has really changed things for many of our patients, even in the up-front and in the relapsed setting for patients. What we’re struggling with now, is, what’s the next best therapy after people have failed these agents? But we really need to clarify those populations, and again, what ends up being very important is, when the drugs have failed the patients, that molecular profile, that mutation profile, again becomes important, because it can be different… 

Andrew Schorr:         

Test again.

Dr. Carraway:            

…at the time of relapse, compared to the time of presentation.

Andrew Schorr:         

So, this is genomic testing, is that what we’re talking about?

Dr. Carraway:            

Mm-hmm.

Andrew Schorr:         

In other words, not genes that affect the color of your eyes or whether you have hair or not, and go bald like your father or mother, but it’s cancer genes.

Dr. Carraway:            

Mostly, yeah genes that are allowing tumors to progress and cause leukemia.

Andrew Schorr:         

Okay, so, you mentioned, Dr. Zeidan, about the immune system. You’re studying that, too, and there’s discussion across the way, and I’m sure you’re involved in it. Are we looking into ways to harness the immune system that let us down when we develop cancer cells in the first place? The aberrant cells proliferated, where you can turn that on and knock the cancer back.

Dr. Zeidan:                 

Yeah, I think that’s definitely a great question, and in an area in which a lot of research is going on. The development of those immune checkpoint blockers, and so the tumors have been a major breakthrough.

Andrew Schorr:         

Yeah, lung cancer, melanoma.

Dr. Zeidan:                 

Yeah, yeah, we’re seeing amazing responses in patients who have very advanced melanoma and lung cancer and other multiple forms of cancer, so the tumors basically, are living much longer and are doing much better. We look at this in the leukemia field, and we say, “Well, we’ve been doing some forms of immunotherapy for many years, bone marrow transplant…“

Andrew Schorr:         

Which is immunotherapy. 

Dr Zeidan:                  

“…which is, basically, a form of immunotherapy, so, it makes sense that some activation of the immune system would lead to control of the leukemia.” We still don’t fully understand, for example, why some patients who get chemotherapy, intensive chemotherapy, are cured and why some others are not, and probably also have to do with their immune system being reactivated in some fashion. So, I do think there is a lot of interest in this area.

I think that some challenges that are unique to this area of study is that acute myeloid leukemia, although we live it every day, is relatively rare, you’re talking about 20,000 patients a year, compared to much more common tumors. So, trying to get the number of clinical studies that you want, especially in this setting, where you have many other agents, has been somewhat difficult to conduct the type of big studies that can give you these results.

The second part, I think, that’s important is that many of these studies that are looking at these, have used different types of immune activators in smaller settings. Sometimes in combination with other agents, sometimes single agents, sometimes at the beginning, sometimes later, and without all of the understanding of the science at the level of the bone marrow and the blood, a lot is actually changing. So, I think some of that is changing. We are getting a better understanding of how all of these processes work, and I’m optimistic that we are going to find a good way to use these agents in some fashion to help our patients who have acute leukemia. 

Andrew Schorr:         

So, Dr. Wang, I have a basic question you must get asked in clinic all the time.

Dr. Wang:

Sure.

Andrew Schorr:         

Family comes in and they said, “Did we do something to bring this on?”, A) and B) “If mom or dad has developed this, do the other members of the family, the younger members, have to worry about that too?”

Dr. Wang:                  

So, that’s a great question, Andrew, and that’s something that was, a primary question, that when people get diagnosed with cancer, is, we always get. I think in the majority of cases, we tell patients that their major risk factor to develop cancer is really their age. As you know most of the cancer screenings that we do, colonoscopies, mammograms, prostate cancer screening, all occur at certain ages. And we know that in the bone marrow of individuals, as you age, these cells age, and they acquire, what we call, age-related mutations, and over time those mutations can contribute to development of acute myeloid leukemia and other bone marrow problems. However, those are due to you being exposed to various things and mutations that occur. They’re not usually due to inherited dispositions. That being said, a small percentage of individuals who develop myelodysplastic syndrome, or acute myeloid leukemia, particularly in younger ages, or ones that have specific mutations may have inherited genetic predispositions.

So, typically what we would do, is we would say, most likely, the typical age of presentation of acute myeloid leukemia is 67 to 70. Most cases are going to be age-related, but it is becoming standard now, that we do a very careful family history, and we look for individuals in the family that might have developed blood cancers, who might have, for example, low platelets or other blood cell abnormalities, and if we see a pattern, we have a protocol at our center. We have genetic counselors, and typically we turn to those experts or to specialized clinics and ask them to do the same thing: to do a detailed family history, and to assure these individuals that is there something that they need to be concerned about?

Andrew Schorr:         

Okay, so, Dr. Borate, so, if somebody is treated with one of these drugs, can you give them some confidence that they can get back to their life for a while, or because it’s acute, it often came on, “phew”, maybe you put them in the hospital right away. Pretty scary. Can things calm down for them? 

Dr. Borate:                 

So, I think that’s something that’s very gratifying, that we as physicians have been able to do in the last few years with some of the therapies that have already been discussed. Instead of putting the patient in the hospital for an extended period of time and telling them that the next six months to a year or two of their lives is going to be, really, time spent in the hospital. Now we can provide options for various therapies that can be at what has been described before as less intensive. That can allow them to have a good quality of life, where they’re spending more time with their loved ones at home, maybe even working, if that’s what they want to. Now, this may not happen immediately, because as you mentioned, acute myeloid leukemia is fairly aggressive, and when we start treating the patient, they are going to experience some side effects as the cells die and the cancer dies. So, we do want patients to be careful in the beginning until we know that we have gotten rid of most of their disease, but once they reach that stable point, we can continue these treatments mostly as outpatients, and allow patients to live a relatively normal life.

Andrew Schorr:         

And I want to thank our doctors for being with us, Uma Borate, from Oregon, Eunice Wang from Buffalo, hopefully you have a good winter, okay? Amer Zeidan from New Haven. And Hetty Carraway from Cleveland. Thank you so much for being with us on Patient Power. I’m Andrew Schorr, bringing you the latest news. Stay tuned as we have a continuing discussion about AML. We welcome your questions. You can always send them to AML@PatientPower.info. Remember, knowledge, and some responsibility and action by you, can be the best medicine of all.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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