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What Does The Viale-A Study Mean For Older AML Patients?

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Published on August 20, 2020

What Do the Viale-A Study Results Mean For Acute Myeloid Leukemia Treatments?

For the typical older patient, aggressive treatments for acute myeloid leukemia may not be an option. Dr. Courtney DiNardo from MD Anderson joins Patient Power co-founder Andrew Schorr to report on the findings of the Viale-A Study. The study combined azacytidine with venetoclax and compared the results to azacytidine alone. This combination offers a new treatment option and new hope for older patients living with AML. Watch to hear the full report.

This program is sponsored by AbbVie and Genentech. These organizations have no editorial control. It is produced by Patient Power. Patient Power is solely responsible for program content.

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Transcript | What Does The Viale-A Study Mean For Older AML Patients?

Andrew Schorr:
Hello, and welcome to Patient Power. I'm Andrew Schorr. Joining me is a leading researcher in AML, acute myelogenous leukemia, Dr. Courtney DiNardo from MD Anderson Cancer Center in Houston. Welcome, Dr. DiNardo. We have a lot to talk about in AML, don't we?

Dr. DiNardo:
Well, thank you so much for the invitation, I'm happy to be here. Yes, of course, lots of things to talk about.

The AML Treatment Landscape is Improving

Andrew Schorr:
Okay. Well we've talked with some of your colleagues and it seems like in the last two, three years, there has been a revolution in AML where there wasn't so much to offer people and including older people with AML, before and now that's changing isn't it?

Dr. DiNardo:
Yes. So, I think two important things to be aware of. One is that the average patient with AML is older. So, a median age of about 68. So, when we talk about kind of the standard intensive chemotherapy that is often considered the curative treatment options, that's really the minority of patients who are appropriate to receive that therapy. So, we have this, often, older patient population, where up until very recently we used lower intensity strategies, things like azacitidine (Vidaza), decitabine (Dacogen), low dose cytarabine (Cytosar-U). They are effective for sure. But unfortunately, majority of patients didn't respond well.

Responses were not that durable, and it was not really seen has a durable curative treatment strategy, and all of that, recently, has changed.

Andrew Schorr:
Okay. Let's talk about that. So, you're a researcher. You've studied and there's a study called VIALE-A which you presented to the world on benefits of adding something, so that particularly these older patients, could live longer and live better. So, tell us about that study, who it was right for, what the results were. And as always, side effects that go with it too.

Dr. DiNardo:
Of course. Yeah. So this was a really exciting study because this was the first one to show in a Phase III confirmatory study, that adding something to azacitidine or any of the other agents we talked about, but in this case, azacitidine, improved both the remissions, the quality of remissions and the long term survival of patients. So, kind of just talking a little bit about the study, it was for older patients with AML who were newly diagnosed. So that criteria to be a good candidate for this therapy were people who were 75 years of age or older, or who had various different medical problems that made the investigator think intensive chemotherapy wasn't a good idea.

A 68-year-old gentleman with underlying heart disease or lung disease or poorly controlled diabetes, things like that, that are significant in many of our adult U.S. and global population. So newly diagnosed older or what we call unfit, that kind of definition of medical unfitness, were eligible to receive either azacitidine with a placebo or azacitidine with a drug called venetoclax (Venclexta). Venetoclax is a pill that is taken daily. It is actually approved for CLL and other lymphoid diseases have had ongoing trials with venetoclax for a long time but what researchers at MD Anderson here, Marina Konopleva, others, Tony Letai in Boston, have identified venetoclax in combination with therapies work incredibly well at getting rid of leukemia cells.

So, this was the conformity study, which built on earlier trial data showing that this combination really seemed to be benefiting patients. Indeed, proved that in this phase III study.

Andrew Schorr:
So basically, though, this was a big deal combining this pill with… azacitidine is a pill as well?

Dr. DiNardo:
Azacitidine is IV right now. It's IV or subcutaneous injection. So azacitidine is also... the trade name is Vidaza and it's given for a week every month. So, the standard treatment, which is also used for myelodysplastic syndromes for older patients with acute myeloid leukemia has often been azacitidine. So patients come into the clinic once... daily for one week every month to get this therapy.

Daily AML Treatment at Home

Andrew Schorr:
Okay but beyond that then, in this study, people can take a pill at home, which would be sort of their daily care, right?

Dr. DiNardo:
Yes.

Andrew Schorr:
And for an older patients, not having to come to the clinic, that's a big deal.

Dr. DiNardo:
Absolutely.

Andrew Schorr:
Okay. What did you find as far as greater benefit with this combination? And also, any management of side effects that went with it?

Dr. DiNardo:
So, just has a rough estimate, the response rates with azacitidine alone were about 30 percent and were 66 percent with the combination. So more than doubling the initial remission rates. The remission rates happen early after about one cycle only. Which means that the majority of patients with leukemia who are going back and forth to the hospital, outside of the azacitidine injections to get their lab counts checked, to get transfusions. This becomes a significant daily grind for patients with leukemia. It's a big burden. Patients going into remission, their counts normalize. So, that is no longer something where two to three times a week, they're traveling back and forth for counts and transfusions.

Overall survival, of course, that gold standard... the whole hope is that we're improving the outcomes of our patients improve from an average of about 9 to 10 months with azacitidine alone to about 15 months with the combination. So, it's incremental benefit but it's significant, especially in patients who have durable impressive responses with this combination. I have patients who have been treated on this initial study since 2014 that are still in my care. It's what six years later in ongoing response. So that's been really amazing to see.

Andrew Schorr:
Side effects with that?

Dr. DiNardo:
There are two main side effects to be aware of, with the combination. One is something called tumor lysis which is where we are doing such a good job at killing off the leukemia cells quickly that as those cells die, they can release chemicals into your bloodstream, and they can kind of start sludging in your kidneys and cause problems. So, there is a risk of tumor lysis when you're using venetoclax-based therapies. In this clinical trial, when patients were managed proactively to prevent TLS, there were no cases of severe TLS occurring at all. So, it's something to be aware of but is not a significant clinical concern if your physician is managing you for tumor lysis prevention appropriately.

Then, the second thing, is what we call neutropenia and neutropenic infections. So, this therapy is very effective at getting rid of leukemia cells. So by the end of that first cycle, that first month of therapy, oftentimes we've gotten rid of the leukemia in the bone marrow but the counts haven't fully recovered yet. So, what we're learning when we're putting these two drugs together is instead of needing to give every four cycles continually, repeatedly, you know you dose on the first week of every month, you get that Vidaza and the venetoclax is continuous.

We often have to hold the venetoclax therapy for a week or two at the end of that first cycle, allow that normal bone marrow recovery to happen. Allow counts to normalize and then oftentimes patients end up needing a shorter duration of venetoclax instead of the pill taken every day continuously forever, you get it for 21 days per cycle or maybe even 14 days per cycle and cycles can extend. Because every patient... we want to make sure you're having that normal count recovery and really kind of not needing additional transfusions or having infections because you're counts are still suppressed.

Andrew Schorr:
Dr. DiNardo, just to sort of sum this up for people, it sounds like for the typical older patient, who wouldn't qualify for some of the more aggressive therapies you have that this is a big deal.

Dr. DiNardo:
Yes. This is the first time in three to four decades that we've had a dramatic advancement in the outcome of our older patients with AML. We have been ... there's been so much excitement and there's so many kind of significant improvements with new therapies in AML, so I don't in any way want to discredit any of the other really impressive discoveries that have been made but kind of across the board for a population of older kind of medically complicated patients to have significant improvement in ... not only their ability to get into remission but to do well, live well, I think is such an important advance in our leukemia care.

Andrew Schorr:
Well, I've seen you quoted on a video where you said standard of care is not okay. So has a researcher, this is what it's all about for you, right?

Dr. DiNardo:
I mean, there's nothing wrong with the standard of care as it is because that's what is important and effective to treat our patients but the role of the clinical researcher is to never say, “okay we're done.” We've done as good as we're going to get and it's time for us all to go home. The point is to always be trying to improve upon that, whether it's improving tolerability or improving outcomes. So this is definitely one of those important advancements.

Andrew Schorr:
Well, I think for patients and family members who are watching, this is an example of science advancing with researchers like Dr. DiNardo and colleagues around the world. So, you, if you're affected by it or someone in your family, ask about it; is there a new combination proven in a phase III trial that really should be brought to bear here that can have great benefit? Dr. Courtney DiNardo, thank you so much for being with us. Thanks for the work you do and keep at it, okay?

Dr. DiNardo:
Thank you. So much. It's been my pleasure.

Andrew Schorr:
Okay. I'm Andrew Schorr, reminding all of us that knowledge can be the best medicine of all.


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