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Can Hypomethylating Agents Be Used for MPNs?

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Published on July 10, 2019

What are hypomethylating agents? Can myeloproliferative neoplasm (MPN) patients benefit from them? Leading MPN expert Dr. Guillermo Garcia-Manero, from The University of Texas MD Anderson Cancer Center, joined Patient Power to discuss studies looking at optimizing the use of hypomethylating agents and the future of combination therapies. Watch now to find out more.

 

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Transcript | Can Hypomethylating Agents Be Used for MPNs?

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.

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:

Hello and welcome to Patient Power.  I'm Andrew Schorr.  So there is a lot that's discussed at the big ASCO conference, American Society of Clinical Oncology, and one of the presenters this year is a leading physician?scientist from MD Anderson, and that's Dr. Guillermo Garcia?Manero. Welcome back to Patient Power, sir. Thank you for being with us.  

Dr. Garcia?Manero:

Thank you, Andrew.  It's an honor to be here.  

Andrew Schorr:

So, sir, for those of us living with myeloid conditions, I know you've been looking at hypermethylating[sic] agents.  We don't really understand that.  How could that possibly lead to better care?  

Dr. Garcia?Manero:

So these are drugs that are approved both for MDS and AML.  We have them now for a number of decades, but what is very interesting to me is that we're still trying to understand how they work, and we are still trying to optimize their use in different conditions because they are kind of agnostic I think to just MDS and AML.  They could have use in other conditions.  

So basically we're still thinking about what is the proper dose on a schedule both in MDS and AML, what are the optimal combinations, and is there a use for other conditions like myeloproliferative neoplasms or other diseases.  

Andrew Schorr:

Okay. Well, let's talk about MPNs for a second.  So I've been talking a lot with subspecialists in that field, and they are talking about the future of combination therapies.  So do you feel that maybe these hypomethylating agents could be in combination with JAK inhibitors or other medicines, antifibrotics, to try to work together to help people in a better way?  

Dr. Garcia?Manero:

I think so. Indeed, as you very well know, Andrew, these diseases are extremely heterogeneous, and they include a number of very different conditions.  So for instance one could take a chronic myelomonocytic leukemia that could be considered as a syndrome in that category.  These hypomethylating agents, both azacitidine (Vidaza) and decitabine (Dacogen), are very effective in CML, and we have actually tested combinations of these hypomethylating agents with ruxolitinib (Jakafi) in this context with actually very nice responses.  

This then can apply to other overlap conditions.  There's a group of disorders that they have both features of MDS and MPN. They may be more or less the (inaudible?) where you could think about the backbone with a hypomethylating agent in combination with another compound, and of course the logical compound would be a JAK inhibitor such as ruxolitinib.  And data actually from Dr. Verstovsek here and Dr. Lucia Masarova at MD Anderson published in Blood last year indicate actually a very high response rate of this type of combination in the specific subset of people with MPN.  

Andrew Schorr:

So is that the future, you think?  We've seen that in so many other cancers, that where we've had one approved medicine, like you mentioned ruxolitinib, that we'll be looking at combinations of drugs that work in different ways to sort of stop the proliferation of the cancer, the survival of the cells.  

Dr. Garcia?Manero:

I think you put it very well, and you maybe actually think two different angles of disease with two tracks that may not interfere on their mechanism of action. I'm just treating actually—this is an anecdote—a lady from another country that came here with advanced transformed MPN with a very large spleen.  Contracted myelofibrotic leukemia transformed from a long phase of p. vera, she's really having a dramatic response to this combination.  I just saw her actually yesterday where probably the ruxolitinib, that for some reason she had never received in her country, decreased her spleen very significantly.  And we're talking like three or four weeks, and she has had a very nice response in the bone marrow with a decrease in her blasts with just one cycle of decitabine. And interestingly actually she was showing signs of portal hypertension, severe ascites.  This is all gone in three or four weeks.  So this is an anecdote, and unfortunately not all patients behave like this, but they can be extremely active.  

And another positive aspect of this is that they are actually very well tolerated, so there is not an additive toxicity profile for this type of combination.  

Andrew Schorr:

Okay.  So just so we understand.  These hypermethylating[sic] agents, the two that you've had for a while, in looking at the combinations azacitidine and…

Dr. Garcia?Manero:

…decitabine.  

Andrew Schorr:

Decitabine, okay. 

Dr. Garcia?Manero:

Now, there is a new compound that we hope that could be approved at some point this year or early next year that is an oral form of decitabine, and potentially also an oral form of azacitidine, so it may be that in the near future we may have actually oral compounds in this class.  They are the same drugs, just orally, but this will make the life of our patients significantly easier.  

I don't know if we have time or not, Andrew, but for instance I can tell you that another classic myeloproliferative disease, chronic myelogenous leukemia, CML, we don't think about these hypomethylating agents, but we use them all the time in combination with TKI in patients with advanced?phase CML like accelerated or transformed to myeloid acute phase of the CML in combination with more advanced PKIs. And other disorders, like for instance refractory anemia with ring sideroblasts and thrombocytosis, so these are rare MPN?like disorders can also benefit from this type of compound.  So the use is actually probably broader than what we conventionally think for these agents.  

Andrew Schorr:

Okay.  So I think the news for our patients, particularly who have more difficult to treat conditions is at a research center such as MD Anderson they're looking at new combinations including with this class of medicines that Dr. Garcia?Manero has mentioned and that could apply to your case.  So if you have a difficult situation this is something to be discussed.  

Dr. Garcia?Manero from MD Anderson, thank you for being with us on Patient Power.  

Dr. Garcia?Manero:

My pleasure. Thank you very much for the opportunity. 

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.