[ Anglais] AML Treatment News: An Expert's Perspective

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Topics include: Treatments

The treatment landscape is changing quickly for people with acute myeloid leukemia (AML). With newly approved options, including enasidenib (Idhifa), CPX-351 (Vyxeos) and midostaurin (Rydapt), it is vital that patients and their loved ones stay up-to-date on treatment news. In this interview, Patient Power founder Andrew Schorr is joined by a leading expert, Dr. Olga Frankfurt, from the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, as Dr. Frankfurt puts recent drug approvals in perspective.

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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 in California.  Joining us from Chicago and from the Robert H. Lurie Cancer Center at Northwestern University where she is co-director of the Leukemia Program is Dr. Olga Frankfurt.  We want to talk about acute myeloid leukemia.  Thank you for being with us, Dr. Frankfurt. 

Dr. Frankfurt:

It is my pleasure.  Good morning. 

Andrew Schorr:

So, Dr. Frankfurt, we've talked about leukemia over the years, but we talked about chronic leukemia, we talked other conditions.  We didn't always have much to say about AML, but tell us, it seems like things are changing fast. 

Dr. Frankfurt:

It is quite amazing.  I do believe that every generation of oncologists think that they are on the cusp of solving, solving and curing the disease, but I truly think we are—we are getting very much closer.  Finally, our ability to treat the leukemia is catching up with our understanding of the pathophysiology and mechanisms of leukemia. 

I mean, for years we know that not all leukemias are made equal.  There are many different disorders with different behavior, different response to therapy and different survival. But finally now other than just being able to tell this to the patient and prognosticate their disease we are able to treat it differently, and this is unbelievably exciting.  Three drugs got approved in the span of couple of weeks, which is really, really, really an amazing time. 

Andrew Schorr:

And you have clinical trials going on too, so it seems like the FDA is working with researchers such as yourself around the world in trying to zero in on the science and move things along knowing people are so sick. 

Dr. Frankfurt:

Absolutely.  We've been involved actually with every of the three drugs that got approved.  We had experience with those drugs, and we had those clinical trials at our institutions, which means we have patients living normal lives and will be cured hopefully even prior to this approval, because they had access to those medications. 

Andrew Schorr:

Let me see if I understand now.  So AML had been a fatal condition, right?  I mean, some people had transplant, right? 

Dr. Frankfurt:

Correct. 

Andrew Schorr:

But barring that, it would shorten your life.  Where are we now with these drug therapies as far as what you alluded to that somebody could actually live okay?

Dr. Frankfurt:

So let's discuss those drugs in a little bit more detail.  So for many forms of acute leukemia, acute myeloid leukemia, transplant still remains the only curative option, but in order to optimize the outcomes of stem cell transplant you need for patients to be in a really good, deep remission. 

So the first medication that got approved was midostaurin (Rydapt), and that is a specific targeted therapy.  There is a specific mutation that's present in subsets of acute myeloid leukemia.  It's called "Fleet 3," FLT3, and it's usually those—the AML that has that mutation has a pretty what people would consider classic leukemia course, very aggressive onset, patients are very sick.  They have high white counts.  They tend to respond to treatment similarly to other forms of leukemia, but they tend to come back.  So the FLT33 positive disease tends to come back before we would get a chance to take patients to transplant. 

So this medication called midostaurin, FDA approved it to be administered in a frontline setting together with induction chemotherapy, okay?  And that drug has been shown to prolong survival of patients, significantly to prolong survival for patients who receive that medication.  So, again, whether you get them into remission and if you are able to take them to transplant or if they're a lot older and transplant is not in their best interest, the survival of such patients is significantly longer.  So that is very exciting. 

Andrew Schorr:

So that's one.  Take us through some of the others now.  You have more armamentarium, if you will.

Dr. Frankfurt:

You do.  We certainly do.  The there is another dreaded subset of acute myeloid leukemia, it's acute myeloid leukemias that arise from the prior bone marrow disorder, MDS, a myeloproliferative disorder.  All patients who received therapy for other cancers like breast cancer, lymphoma, they develop what was called secondary acute myeloid leukemia.  Those are terrible disorders that do not respond well to chemotherapy. 

There is a medication called cytarabine and daunorubicin (Vyxeos) that again just got approved last week, and it is a chemotherapy, right, where the first medication is a targeted therapy, is not a chemo, this is still a chemotherapy.  But the interesting part about this chemotherapy is that it's standard drugs, two drugs that we normally use for acute leukemia, but the concentrations of those drugs are specifically calculated and play in those two—and at that specific concentration they are placed in the liposomal molecule. 

So in clinical trials, it was shown that this specific concentration of one drug to another, that ratio, it appears to have a very significant cell kill, of leukemia cell kill.  So that medication has been shown to significantly improve responses and duration of the response for patients with those forms of acute myeloid leukemia. 

And what I find very, very exciting about this drug is that those patients, first of all a lot—many more patients on the study drug were able to receive a stem cell transplant, right?  So to go to stem cell transplant, which means they are in remission in order for this to happen, and the outcome of those patients was better than the patients who received the standard chemotherapy, which tells me that there's possibly a deeper remission, a better response to this treatment, and that's why it leads to better outcomes after stem cell transplant. 

Andrew Schorr:

Okay.  And just to wrap up on that one, so basically what's been perfected is a delivery system to deliver kind of a bigger bang to the cancer cells, right? 

Dr. Frankfurt:

In a way.  In a way.  The actual amount of chemotherapy is less than we would have been giving the way we standardly administer induction chemotherapy, but your bang for the buck is significantly more. 

Andrew Schorr:

Targeted. 

Dr. Frankfurt:

Yes. 

Andrew Schorr:

Targeted.  Okay.  So now you mention there have been three drug approvals. 

Dr. Frankfurt:

That's correct. 

Andrew Schorr:

So we've talked about two.  What's the third? 

Dr. Frankfurt:

The third one is also a targeted therapy.  It targets a specific mutation.  It's called IZH2 mutation, IZH2.  And, you know, it's not—it's not a very prominent mutation in AML, around 15 percent, between 9 and 18 percent of patients depending on the study have that mutation, but in patients—so the clinical trial—what's unusual about this is the FDA approved this drug based on the results of a Phase I, II clinical trial.  Phase I is typically first in humans, right, and the second one is already looking for efficacy, but it's early type clinical trial.  Usually the FDA requires a Phase III clinical trial, a randomized study to show the improvement. 

Here the results were so significant that FDA felt compelled to approve the drug based on results of a Phase I, II clinical trial.  Not unheard of.  I mean, it happened before, but distinctly uncommon for this to happen.  So it's an oral medication and in patients with relapsed/refractory disease, meaning patients who failed other forms of therapy, there was about a 25 percent remission rate, which again in a single agent, oral medication, well tolerated, it is remarkable. 

Andrew Schorr:

Wow.  So that's what you have approved now with the FDA kind of moving fast, but you have trials going on.  So are there other things shaping up? 

Dr. Frankfurt:

Absolutely.  Absolutely.  First of all, those drugs got approved pretty rapidly.  We're still working on figuring out how do we sequence that, who do we give it to, do we combine this medication with other things, what is better?  There's still so many unanswered questions, so that obviously is being figured out right now.  There are multiple clinical trials going on all over the country and all over the world figuring out what is the best way of administering those medications. 

And, of course, there are other medications.  There is multiple fludarabine (Fludara) inhibitors that are going on.  There's IDH1 inhibitors.  There are other targeted therapies aimed at various mechanisms important in the development of leukemia.  So there's a lot of stuff going on. 

Andrew Schorr:

Okay.  So we have patients and family members who are watching, and they say, oh, my God, I've been diagnosed, often an older person…

Dr. Frankfurt:

Disease of older adults, correct. 

Andrew Schorr:

…diagnosed with a very serious life-threatening condition.  What hope should I take from what you're saying? 

Dr. Frankfurt:

Patients need to be seen in an academic center where doctors have access to novel therapies that are either available clinically or not available clinically and based on the patient's characteristic, right?  We need to know the details about their disease.  Almost everybody does next-generation sequencing at the time of the diagnosis to define the disease to the smallest detail possible to find out what is the optimal treatment.  So I think patients need to be seen in an academic center.  And I'm biased, I realize that, but—and optimal treatment must be—will need to be decided based on their disease characteristics. 

Andrew Schorr:

Well, let me put in a pitch for something.  So we're a big believer in a term you know well, precision medicine, and I think for our audience of patients and family members it's really getting to the right specialist such as Dr. Frankfurt, and there are others around the country and around the world who specialize in acute leukemia, and having the right tests. 

And you mention next-generation sequencing, getting this testing to know what is your version at that time of the AML, right?  Because you're talking about targeted therapies that apply to one group of patients but may not apply to another, so you need to know the what, right? 

Dr. Frankfurt:

That is correct.  That is correct.  And, again, there are so many questions remain unanswered.  I don't want sound like we are done.  We are far from being done, but I can't compare the world of leukemia therapy now compared to even, you know, 15, 16, 17 years ago when I was starting just based on the conversations that I have with my patients telling them what needs to happen for me to determine what's their best treatment option, whether it should be a clinical trial, whether we have good drugs available, you know, clinically.  Those conversations became a lot more sophisticated and a lot more detailed, and that's how I know that things are hugely changing, because every year I have to tell something different. 

Andrew Schorr:

Okay.  So for patients who might come to you today, this week, you—it sounds like—I don't know that nobody's—you're not always smiling because we're talking about very serious illness, but it sounds like you have things to offer and for the family, they can take hope from that. 

Dr. Frankfurt:

Exactly right.  It is exactly right.  The world is different, the treatment is different, and even the medications that we have today not only they're effective, they are oral medications.  They can be taken at home.  Yeah, it's a different world. 

Andrew Schorr:

Okay.  Well, I want to thank you and your colleagues, researchers around the world who do clinical trials and patients who participate, to get us to this point.  I don't always say complimentary things about them him, but I will this time, Dr. Pazdur and some of the others at the FDA.  They are following the evidence and moving things along quicker.  Thank you, FDA in collaborating with the researches and the companies such as yours.  Thanks to the companies that have been investing in all this and working with researchers so we can do this.  So, Dr. Olga Frankfurt, thanks for updating us. 

Dr. Frankfurt:

It's my pleasure.  It is my pleasure.  I'm very excited to talk about these new things.  It's great. 

Andrew Schorr:

Okay.  Well, we'll check in again and all the best to you and Dr. Altman your co-directors at the Leukemia Program at Robert H. Lurie Cancer Center at Northwestern.  And let's work for that cure, okay?

Dr. Frankfurt:

We're on it.  We're on it.  Thank you so much, Andrew. 

Andrew Schorr:

Thank you.  I'm Andrew Schorr.  She's in Chicago.  I'm in California.  Remember, knowledge 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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Page last updated on September 3, 2019