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Understanding New Categories of MPN Therapy

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Published on January 21, 2016

Transcript | Understanding New Categories of MPN Therapy

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.            

 

Dr. Michaelis:

Dr. Michaelis, let me ask you now, we get into research. So now, where are we headed? And we’ve alluded to combination therapies. We’ve alluded to other JAK inhibitors.  So why don’t you begin to help us with that? And we’ll get everybody involved because there’s a lot there, but why don’t you tackle this first, Laura?

Dr. Michaelis:     

Sure. So when I talk to patients about the direction that research is taking in myelofibrosis in particular, but the MPNs in general, the first is can we improve on the way that we’re using JAK inhibition?

So the current one that you all know is ruxolitinib (Jakafi), which has improved, which, again, blocks some of those downstream signals that sort of make the bone marrow irritable and active and vulnerable to additional mutations.

 So there are some limitations to using ruxolitinib as has been mentioned. And that includes the fact that it can lower red blood cells, and it can lower platelets. So the next generation of these JAK inhibitors are aimed at doing what ruxolitinib does, improves symptoms, decrease the spleen size, hopefully make patients live longer but without lowering the blood counts as much. 

They come with their own little side effects, but there are currently three or four that are working their way, that are percolating through the clinical trial pathways to try and get to the point where they can be used either after ruxolitinib hasn’t worked or instead of it.  So they will be competing.  So that’s one category of clinical trials in myelofibrosis is alternative JAK inhibition.

The next category is in the anti-immunomodulators. So we’ve mentioned lenalidomide (Revlimid).  Lenalidomide is from myeloma.  It was sort of proven in myeloma as related to thalidomide (Thalomid). 

And what it does is, theoretically, calm down some of the—well, I’m not sure anybody actually knows how it works. But it may decrease some of the immune problems of the chemicals inside the bone marrow, and it may be able to be used alone or in combination. And there is some work being done on those drugs, which have been pointed out or called the IMIDs.  The next are anti-fibrotic drugs.  There’s a medical condition called pulmonary fibrosis where it’s rare.

But it can cause just progressive scarring down of the lungs. And due to some innovative thinking, people thought why not use a medicine that had been thought about used in pulmonary fibrosis to treat fibrosis that evolves in the bone marrow with the idea that this chemical milieu is making the bone marrow soil, the stroma there, not work particularly well, not support cell growth and cell health.

And so there are currently some studies going on on two drugs that are called anti-fibrotics.  We’re trying to get rid of the fibrosis.  Interferons, as Dr. Verstovsek talked about, these are non-chemotherapy, but they are employed to decrease the inflammation of the bone marrow and maybe the whole body. And maybe some of that inflammation is helping to support the negative cancer cell. So either alone or in combination with ruxolitinib or the other JAK inhibitors, maybe we can hit two things at once.  There are also these things called pathway inhibitors. 

These identify differences between the bad stem cells and the good stem cells and say well, these bad stem cells make too much hedgehog inhibitor or have changes in the way they kill of dying cells called telomerase.

So they’ve identified differences between the bad cells and the good cells. And they’re going to use medicines that have a predominant effect on the bad cells rather than the good cells, sort of driving a wedge and killing off the bad clonal cells. Those come in the forms of telomerase inhibitors or imetelstat is the name of the one that’s percolating up the most. 

Medicines that come under the group of hedgehog inhibitors, named after Sonic Hedgehog, for example. So there are classifications of different things that are being tested. And then, just to make things more complex, we’re looking at layers of therapy.

Maybe things will work if we put a tyrosine kinase inhibitor alongside a Jakafi.  Maybe we need to do interferon and lenalidomide, for example.

So these combination therapies are also being looked at. So when you think about a clinical trial, the reason that all of these exist is because the disease is very heterogeneous.  Some people will have myelofibrosis and live for years with minimal impact on their life. And some people have it had have very acute, fast development of symptoms.  And our job, along with you, is to try and figure out early on are you going to be in the camp that’s indolent that we can watch and wait and continue to look for new or innovative therapies to use?

Or are you going to be in the camp of one where this disease is going to move a little bit faster, and we need to think about moving in and interfering in the disease much more quickly, especially when you’re thinking about transplant?  Understanding how your disease is going to behave in the future makes a big difference before we jump in with a risky but, sometimes, incredibly important therapy like transplant.

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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