How Does Inhibitor Therapy Work to Treat Myelofibrosis?

How Does Inhibitor Therapy Work to Treat Myelofibrosis? from Patient Empowerment Network on Vimeo.

What is inhibitor therapy? Dr. Joseph Scandura reviews approved JAK inhibitor therapies and explains how they work to treat myelofibrosis.

Dr. Joseph Scandura is Associate Professor of Medicine and Scientific Director of the Silver MPN Center at Weill Cornell Medicine. Learn more about Dr. Scandura, here.

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Transcript

Katherine Banwell:

How does inhibitor therapy work to treat myelofibrosis? 

Dr. Scandura:

So, the therapies that we have now that are approved therapies that are in this class are  ruxolitinib (Jakafi) and fedratinib (Inrebic) 

Both of these agents act to block signaling through a protein called JAK2. You can think of JAK2 as being part of the antennae system that a cell uses to communicate with the rest of the body. And so, our blood-forming cells have a lot of input from the body saying, “Okay, we need some of these kinds of cells, we need some of those kinds of cells,” and it’s a very adaptive system. And JAK2 is involved in a lot of the signaling in this as part of the antennae system.  

And what happens in the myeloproliferative neoplasms is that signaling is a bit excessive. 

And so, it’s like the volume is turned up too loud and the signaling is causing the cells to do things, make too many cells, make the wrong kinds of cells, and JAK2 is part of that signaling system. So, these inhibitors kind of help turn down the volume of the signaling in these blood-forming cells. They are drugs that have good activity in improving symptoms, they have great success in reducing the size of the spleen, they can be useful for a few years to many years. They are not curative therapies. We don’t think of them as therapies that change the course of disease, but they certainly have an important role in helping people feel better. There are other inhibitor therapies that are in clinical development. 

So, clinical trials of some of these drugs have really impressive activity, but none is approved yet by the FDA.  

I hope and expect we’ll have a couple more drugs available in the coming years. And there’s a lot of excitement in clinical trials in terms of some of the activities that are being seen, and really quite tolerable therapies, so not a lot of side effects for patients. And so, I think it’s kind of an exciting time for physicians and for patients and a lot more options now and, I think, a lot more options coming down the line.

Which Gene Mutations Impact Myelofibrosis Treatment Options?

Which Gene Mutations Impact Myelofibrosis Treatment Options? from Patient Empowerment Network on Vimeo.

Are there specific mutations that may affect myelofibrosis treatment choices? Dr. Joseph Scandura explains the factors that are considered when deciding a myelofibrosis therapy, including a discussion of high-risk and low-risk disease.

Dr. Joseph Scandura is Associate Professor of Medicine and Scientific Director of the Silver MPN Center at Weill Cornell Medicine. Learn more about Dr. Scandura, here.

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Transcript

Katherine Banwell:

Are there gene mutations that affect myelofibrosis treatment choices? 

Dr. Scandura:

Yeah. So, you know, the primary mutations in JAK2 or CALR or MPL in myelofibrosis aren’t that helpful in guiding therapy.  

And we look at the other genes for co-ocurrent mutations and those, as I was mentioning before, can come into one of two categories. So, there are a number of genes that we know tend to confer a higher risk, and so we call those high molecular risk mutations. And people who have higher molecular risk tend to have a more aggressive disease. 

Now, I want to add a word of caution because when we talk about patients and risk, we’re talking about groups of patients. For any individual, everything kind of boils down to it happens, or it doesn’t happen. And so, there’s nobody is 50 percent dead in five years, right. You either are or you’re not. And so, when we talk about risk, then we’re talking about risk of bad things happening like death or other complications of the disease, we’re trying to guide treatment decision-making and guided discussion based on a chance.  

But all of those things, for any individual, there are people who have high risk who do quite well for a long period of time, and people who don’t have high risk who don’t do as well as you think they should. And so, it’s a part of a conversation, it helps guide discussion, but it is not something carved into stone, and nobody has a perfect ability to predict anybody’s future. 

And all of these things are our best tools to estimate, but they are not a future; they are a possibility. And so, people who have higher molecular risk, we might think about more aggressive treatments than people who have lower molecular risk.