ASH 2018 AML Treatment and Research Updates From an Expert Roundtable

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Topics include: Treatments

As part of Patient Power’s on-site coverage of the 2018 American Society of Hematology (ASH) annual meeting in San Diego, founders Andrew and Esther Schorr hosted an expert roundtable to review acute myeloid leukemia (AML) news announced at the conference. AML experts, Dr. Sangmin Lee and Dr. Ellen K. Ritchie, both from Weill Cornell Medicine, and Dr. Tapan M. Kadia, from The University of Texas MD Anderson Cancer Center, discuss highlights from the meeting in what they call an “AML treatment revolution.” The panel shares new drug approvals, innovative treatment approaches for both primary and secondary AML, emerging research and more. Tune in to find out the latest news. 

This is a Patient Empowerment Network program produced by Patient Power. We thank Daiichi Sankyo and Jazz Pharmaceuticals for their support.

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Transcript

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. I’m Andrew Schorr from Patient Power. Welcome to our program, from San Diego and the American Society of Hematology meeting, where the people from around the world discussing the latest in blood-related conditions. And there is a lot of discussion given new drug approvals and lots of research in acute myeloid leukemia. And it gives new hope to patients and their families dealing with this acute condition. So, joining me is Esther Schorr. And, Esther, you’ve been talking to people. And we have a wonderful panel we’re going to meet, in a second.

Esther Schorr:   
I have. And, especially with the more acute conditions that these wonderful researchers and clinicians are working with, I think that we need to discuss how family members, care partners, caregivers, what active role they need to play in sort of the rapid fire beginning of getting treatment.

Andrew Schorr:
How you want the best yourself for a loved one. Let’s meet our panel. So, I’m going to have you introduce yourself, so we get your titles right and your institution, please.

Go right ahead.

Dr. Lee:
So, I’m Sangmin Lee from Weill Cornell Medicine. And I’m part of the Leukemia Program. And I’m an Assistant Professor there. And I focus on myelodysplastic syndrome and acute myeloid leukemia.

Andrew Schorr:
Okay. And next to you is a colleague of yours.

Dr. Ritchie:         
My name is Ellen Ritchie. I’m an Associate Professor of Clinical Medicine and the Assistant Director of the Leukemia Program at Weill Cornell Medical College. I treat all myeloid malignancies. And I also treat acute lymphoblastic leukemia.

Andrew Schorr:
Okay. And both, two New Yorkers. And now, let’s go to Texas.

Dr. Kadia:            
I’m a Texan but a former New Yorker. My name is Tapan Kadia. I’m currently Associate Professor in the Department of Leukemia at MD Anderson Cancer Center in Houston, Texas. My practice is based on research and clinical work in acute myeloid leukemia, MDS. I also look at bone marrow failure syndromes. And I’m glad to be here, so thank you.

Dr. Ritchie:         
Thank you for having us.

Andrew Schorr:
So, Dr. Ritchie, I’m going to start with you for a second. So, are we right? It seems like someone’s head can spin, with all of the new drug approvals, and then, also trying to make sense of what’s right for what patient. So, how much have things changed in AML?

Dr. Ritchie:         
Well, AML used to be a really simple disease, because we had two drugs, and that’s how we treated patients. Now, it’s a more complicated disease, partially, because we’re learning a lot more about this disease molecularly. And there are new targeted agents, which have been recently approved, in the last year, for the treatment of AML. Many of them, just recently, in the past few days. Gilteritinib, (Xospata), which is a second FLT3 inhibitor was in there last week. A lot of these drugs are drugs that fall into two categories. Some which target mutations that may be relatively infrequent like IDH1, IDH2, FLT3.

And these are for those specific populations who have those particular mutations.

There are also drugs that are more blanket that cover patients who have really any abnormality, which are added to standard therapy like venetoclax (Venclexta). Venetoclax was initially approved for the treatment of CLL and has recently had a new label to add to low-dose ARA-C or to hypomethylating agents, for the treatment of AML. And that’s an exciting new development where the response rate with hypomethylating agents goes from about 40 percent to 70 percent. So, it’s a real advance, for those particular patients.

Also, in the really older and frail population, I always have problems saying it, glasdegib (Daurismo), which is really a drug, which is directed at the leukemic stem cell together with low-dose ARA-C. These have been approved really for patients who are a little bit more frail and older.

And it’s a regimen that is more easily tolerated by that age group.

Andrew Schorr:
So, just a follow-up. So, how much of a difference - the FDA approves effective therapies effective therapies, which, hopefully, make people’s life better and longer. So, is that the hope for our viewers watching that whether it’s themselves or an adult parent or grandparents that they can have a better, longer life?

Dr. Ritchie:         
Well, there are a lot of aspects to leukemic care. It’s not only having a longer life but having a higher quality of life. So, it’s the quality of life that you have, as well as the length of life that you have. So, just to put it in reference, standard induction chemotherapy, where we use two drugs, daunorubicin and cytarabine (Cytosar-U), which my father used to use when he practiced medicine, and those days are—it’s an old combination. But it really requires the patient be in the hospital for 30 days. And these patients are sick. And they require transfusions.

And most of them require antibiotics. And they don’t feel very well, and it’s a difficult time. So, for older patients, are you really willing to spend a month of your life or maybe two months of your life where you really feel terrible in the hospital? That’s not necessarily something that you want to do. So, part of the breakthrough is not just that we may improve overall survival, which we don’t really know, until it’s out in the community, and we see how it works. But whether we can improve the overall quality of life of older patients who have AML. So, and rather than being in hospital, you can have your therapy, in an outpatient setting.

And rather than it being all intravenous, you might have an oral medicine that you could take at home, like you do your hypertension pill, really, for your AML. So, these are really important advances, because it enhances the quality of life of patients who have acute leukemia.

Esther Schorr:   
Well, and it also sounds like you referenced that a lot of the patients are older with this. And I just can’t imagine what it must be like, if you have two much older people, and one person is, as you mentioned when we were talking earlier, one is out of commission.

The other is not only going to need support from family, but if their partner doesn’t have to be in the hospital to be able to at least be home, there’s some level of support there.

Dr. Ritchie:         
Right. Well, you guys can chime in. But a typical situation, really, is two older people who are living together where they’re doing just fine as a symbiotic couple. But they both have their illnesses or both have their problems. But once you take one person out of the picture, and that person is very, very sick, it can be very difficult for the other elderly person to actually handle all of the stress of taking care of themselves and all of the stress of taking care of another person. So, one of the key factors, I think, in overall survival and quality of life in patients who are older who have AML is having a caretaker who is reliable for them.

And that may be your child.

It may be your sister. It may be a good friend. But there has to be someone in your life, beyond just your spouse, who can be a caretaker for you for a successful therapeutic result.

Dr. Lee:
And one thing that is great about the medicines that are coming out are that they’re very well tolerated, especially the IDH drugs and venetoclax. They’re very well tolerated. You can do it outpatient. So, for a lot of older patients, as you know, if you stay in the hospital more, you’re exposed to infections. Your performance status may decline. So, patients actually do better with an outpatient therapy. I think that’s beneficial.

Esther Schorr:   
And also older people. I have two aging parents, thank goodness doing well. But they’re in their 80s. And just driving to the clinic is a big event. But if you’re having to do that every day for treatment or going to visit.

Dr. Ritchie:         
Right. And we don’t want sick people driving necessarily to our clinic because, if your hemoglobin is 7, and your platelets are low, you’re not in the best situation to be reactive to the problems of traffic and cars.

So, transportation is also a real issue, I think, when patients are older and coming in for treatment.

Andrew Schorr:
Dr. Kadia, so we’ve mentioned a couple of these cancer genes. IDH, FLT3, I think. So, these are oncogenes, right?

Dr. Kadia:            
Right. So, what’s been great, and I think this has been greatly summarized by my colleagues, but we’ve had sort of a revolution in how we treat AML and many cancers, but particularly AML and the liquid tumors. With the advent of what we call next-generation sequencing, we’re able to really get the mutations and the data from the leukemia cells. We find that there are recurrent mutations. Mutations are changes in the DNA that happen over and over and over again, in different people with leukemia. So, it made us realize that, if these mutations keep happening in AML, they must drive the AML.

There must be something about them that makes the AML happen. And, in fact, that’s the case. So, in a handful of those mutations, things that people have really studied, we now know that things like FLT3 or “flit 3” is a mutation that really drives proliferative AML. And so, people said, well, if that drives it, can we develop a drug target inhibitor of that mutation to shut the leukemia down? And indeed we can. We used to use a drug call sorafenib last year, over a year ago. A drug called midostaurin (Rydapt) was approved with chemotherapy in the frontline. And just recently, as was describe, just a week ago, gilteritinib was approved in patients who have the FLT3 mutation, but they’ve had relapsed disease.

So, that’s just one example. The second you said IDH, right, isocitrate dehydrogenase, another mutation. We didn’t know what it meant. But people worked and worked and figured it out. And they found out there’s two mutations, an IDH1 and an IDH2 mutation. Each of those drives that particular subset of leukemia. And it turns out you can make inhibitors to each of those, and they work. An oral medication you take once a day for people with relapsed disease actually works.

And it doesn’t work like regular chemotherapy. We describe intensive chemotherapy. You put them in the hospital, their hair falls out. They have mouth sores and diarrhea and nausea and vomiting. We don’t see that, with these pills. We do see some side effects. And, certainly, the patient and the family member need to recognize those side effects. So, there are side effects. But they’re different. They’re more tolerable. They’re more manageable. And so, that’s what we’ve been able to do, get people home, take these medications, and target these specific mutations.

So, among the many mutations we’ve discovered, we found drugs for probably two to three of those targets. But we also found that some of these mutations will predict for responses to other drugs like venetoclax.

Andrew Schorr:
Let’s talk about testing. How do you know?

Esther Schorr:   
I was just going to say it really sounds like you have to be tested.

Dr. Lee:
Yes.

Esther Schorr:   
To know where you fall.

Dr. Ritchie:         
And I think that’s one of the big barriers right now that I feel the insurance industry has not really caught up to what it is that we’re doing in AML. So, every patient who is getting or has a suspicion that patient has AML, that patient, when they have a bone marrow biopsy and they see a doctor should have a next-generation sequencing sent.

The problem is this costs thousands of dollars. Now, some insurance companies are not—they don’t really care or aren’t really cognizant of the quality of the different NGS panels. And they make deals to cover with one or not cover at all. So, it can be a hassle for the patient. And it can be thousands of dollars expense. So, that’s something that I think the whole industry is working on to try and enlighten insurance companies and to make them pay for this particular sequencing. MD Anderson has their own in house. And you probably have worked out a deal with insurance companies.

Dr. Kadia:            
No, we have. So, I think more and more, insurance companies are beginning to realize that this is a part of the disease treatment. If you have pneumonia, you’re going to get a chest X-ray. If you have AML, it’s becoming standard.

It has for years. We do FLT3 mutations. We do something called NPM1 mutations. For years, we’ve been doing this in AML. Now, what they need to realize is that we need to expand that to what we call a sequencing panel, which are 80 different genes, which are commonly mutated. Why? Not just because we’re interested and we’re curious, but because these mutations play an important role in telling the patient this is your prognosis. And this is the drug that we’re going to treat it with.

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Page last updated on July 2, 2019