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Can MPN Patients Develop Resistance to JAK Inhibitors?

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Published on April 19, 2016

"Are JAK inhibitors rewriting the natural history of the disease and is there any evidence that you can develop a resistance to JAK inhibitors?" asks Patient Power MPN community member, James, in this Ask the Expert segment. MPN expert Dr. Naveen Pemmaraju of MD Anderson Cancer Center answers both questions, and he comments further on clinical trials as well as other options beyond JAK inhibitors.

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Transcript | Can MPN Patients Develop Resistance to JAK Inhibitors?

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:    

Dr. Pemmaraju, here’s a question we got from James.  He writes, “Are JAK inhibitors rewriting the natural history of the disease, and is there any evidence that you can develop a resistance to JAK inhibitors?” So two questions: first the natural history and then do they wear off?

Dr. Pemmaraju: 

What a great question.  I think for the first part—are JAK inhibitors rewriting the natural history—I think absolutely yes.  So far as you well know and as our viewers know, there’s only the one FDA-approved JAK inhibitor, and that’s ruxolitinib or Jakafi or Jakafi, but several others in various levels of Phase I through III testing. But at least with the experience we have now recently updated at ASH, the five-year update, it does show that not only are JAK inhibitors helping in terms of symptom relief—very important for our patients—spleen size reduction also very

important, restoration of blood counts; but also let’s add a fourth factor, which is improvement in terms of overall survival. 

This was something that was not known and actually was doubted in the beginning phases of these drugs, but we are seeing that to be both durable and a real effect five years out.  So that’s a very exciting prospect. 

 

For the second part of the question—resistance—boy, that’s a hot topic research area as you know.  I do believe that we will likely stumble and find these resistance mechanisms.  As of this taping, we don’t have specific ones to point to, but I will give you a couple of different parallels.  One is in CLL with the ibrutinib (Imbruvica) and the BTK story, which there are point resistance mutations that have been shown in the New England Journal and also in the FLT3 experience with AML where there’s a point mutation called the DA35 that was found early on. 

So while we don’t have a lot of these yet in our field, I do think that we may find those, and so active research is going on there.

Andrew Schorr:                  

Hmmm, so for a patient who is taking one of these drugs, do they have a fear that that will lose its effectiveness for them and worry that there’s not something else?

Dr. Pemmaraju: 

Well, what a great question.  Right—so the first part of it is unfortunately as in any cancer and in any cancer therapies there is that chance that a drug has effectiveness and loses it over time.  Whether that’s a definitive resistance mechanism that we and the scientists can identify—it may or may not be there—but certainly clinically for the patient and for us the provider we know that hey, the drug isn’t working.  The spleen is getting bigger, and the symptoms are returning.  The blood counts are not proper.

But the second part is very important, which there is a lot of hope.  Even though there are not other FDA-approved drugs for our patients with MPN, gosh there are a lot of clinical trials that are going on, which organizations such as yours are instrumental in making sure that people are aware.  Two, there are other off-label, off-protocol standard therapies that we and others have used as well.  So we want our patients to know that clinical trial enrollment is always the ideal option, but not everyone can make it to a clinical trial.  So I would say yes, they are a hope, and there are other options out there.

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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