Controlling JAK2 Inhibitors

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Topics include: Treatments and Understanding

Dr. Jorge Cortes, a renowned leukemia specialist at MD Anderson Cancer Center, discusses JAK1 and JAK2 inhibitors, how these drugs work in patients with mutations, and how they impact those without mutations. Cortes explains the benefits of these drugs, including symptom improvement, but he also makes clear there is much more to be learned about the JAK family.  Dr. Cortes encourages patients to work with their providers to make sure they are receiving doses that balance both the benefits and the side effects of these drugs.

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Please remember the opinions expressed on Patient Power are not necessarily the views of MD Anderson Cancer Center, its medical staff 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.

Dr. Cortes:

Say, okay, it’s not normal that this stays on all the time. We need to turn it off. Well, that led to the development of these JAK2 inhibitors. And there’s been a sequence of several of them that have been investigated. Some of them have not worked as well as we thought they could. Ruxolitinib (Jakafi) was the first one to make it all the way to the point where it was approved by the FDA. And it’s been around now for, you know, a couple of years or so. And that’s the function. It does block that function of the JAK2. Now the JAK is a family.

There are other proteins that are similar. There are JAK1 and JAK2, and it’s not very specific. It doesn’t only block JAK2. It blocks also, JAK1, for example, and that has other functions. But that’s what these drugs do. And now, very important, the drug works. It doesn’t matter if the JAK is mutated. It has that abnormality that has it always on. It can also work on patients who do not have that change. They’re not at that abnormality. Why?

Well, because even if it’s not affected, you know, there are these abnormal signals that are keeping it on. The protein, itself, is not malfunctioning. But the signal is coming all the time that’s keeping it on anyway. So that’s why we see that, the response can happen even if you do not have a JAK2 mutation. And that’s very, very important because sometimes you hear this perception that it is for the JAK patients that have the JAK2 mutation. No, it’s not. It is for those patients, but it is also for the patient that did not have the JAK2 mutation.

Now what does the drug do? Of course, for many of you who are taking it, you know that. And it has significant benefits, in particularly two areas. It shrinks the spleen very nice. You know, patients that have a very, very large spleen, in a majority of patients, have a shrinking of the spleen—some of them, a lot, to the point where we don’t feel it anymore—some of them, less so, but enough that they can feel, already, some benefit. And with that, there are other benefits that come. You don’t feel the discomfort.

You can eat better because, keep in mind, the spleen is there and sitting right next to your stomach. So when the spleen is very big, your stomach, which is like a little balloon when you eat, it, you know, it takes the food. If there’s something blocking that, your little balloon, that’s why some of you may eat very, very little, and you feel like you ate, you know, a Texas size steak. So it shrinks the spleen very nicely. The other thing that it does is that improves the symptoms very well.

And Dr. Mesa has been outstanding in giving us the tools to measure this very, very well. And we see all these different symptoms, some that have to do with the spleen but some that having nothing to do with the spleen. And it improves the symptoms of the patients. We’re still trying to learn what else can the drug do. You know, can it completely eliminate the disease? For example, can it correct that scarring in the bone marrow? And we’re starting to learn that in some patients, at least, it appears that it can do that over time. It doesn’t happen right away.

Like the spleen and the symptoms, those happen quickly. But the improvement in the scarring, it may be that it happens in some patients over time, long, you know, much longer time. Does it take away the disease completely? Yeah, it’s a much more difficult question. I don’t think we have the answer yet. One of the things that we see that when we measure the cells that have the mutated JAK, and they don’t have the mutated JAK—so being the mutated ones, being the bad the ones.

We see that there are fewer of them, so there is at least some change in the balance. If not to eradication of the disease, there seems to be a change in the balance of good versus bad cells. So it definitely does some things that go beyond just the symptoms. And one important thing that we’ve seen is that the patients that have taken this medication have lived longer than the patients who have not taken this medication. And those initial benefits of being able to eat better and feel better and all that have been very beneficial.

And that certainly can help some patients who would otherwise been, you know, not even able to eat or move or anything. And, unfortunately, because of that some of them, you know, pass away in a shorter period of time. So that’s what these drugs do. Now there are other drugs under development. We are hoping that, in the near future, we have others like ruxolitinib or Jakafi. You know, even when they work in somewhat the same way, it’s just like antibiotics. Not all the antibiotics work the same way.

And sometimes, you know, having a different one may help a patient that was once stopped working or something. One quick final word about this drug—one of the things that you see and some of you may have experience, when you take Jakafi, your red cells or your platelets may drop. And that’s one of the things that we see in some patients. It tends to be more at the beginning. And then over time, it tends to become stable and many times even to correct itself, at least, somehow. So that’s a problem.

But if you think about what we explained earlier, the fact that when these growth hormones, whose function are to stimulate the production of red cells and platelets, when they find their receptor, they start, remember I told you, it actually is the spark that starts, you know, lighting up your bulb.

Well, that works whether JAK is mutated or not mutated and whether it’s normal or abnormal. You know, that spark, you’re always going to need. And if you’re going to blow up that spark, there’s going to be a bit of an effect on your normal production of red cells and your normal production of platelets.

So, in a way, it’s part of what this drug is supposed to do. Of course, in this case, it affects in a way we don’t want it to affect. We’re working on ways to try to go around that, which could be either make drugs that have less of that unintended consequence or combine it with other drugs that may help those, counterattack that and improve their hemoglobin or their platelets, adjust the doses, very, very important. That’s something that needs a lot of attention.

Work with your doctors to see that they’re getting the dose that has a good balance and benefits and these side effects. So there are things that we can do to work with that, but it’s something that we see in some patients with these drugs.

Please remember the opinions expressed on Patient Power are not necessarily the views of MD Anderson Cancer Center, its medical staff 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 April 20, 2014