[ Englisch] New Horizons for Interferon Therapy in MPNs

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Topics include: Treatments and Understanding

As part of our coverage of the 2015 American Society of Hematology annual meeting, Dr. Richard Silver joined Patient Power to discuss interferon therapy for the treatment myeloproliferative neoplasms (MPNs), specifically myelofibrosis and polycythemia vera.  Dr. Silver explains interferon, how it works, and the potential benefits of small doses of interferon therapy for MPNs.

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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:    

Andrew Schorr on location at ASH 2015 in Orlando, Florida.  I'm standing with Dr.  Richard Silver from New York City from Cornell Weill.

Dr.  Silver:            

Weill Cornell. 

Andrew Schorr:                  

Weill Cornell.  I always want to get it right.  This man has been devoted to us patients with MPNs at least 45 years.  We wanted to talk to him about an area of treatment that has been around for a while and continues to improve in the prospect of improving even more to make a difference for us.  I'm talking about the use of interferon, Dr. Silver. First of all, help us understand what interferon is. 

Dr.  Silver:            

Interferon is a cytokine, which means it’s a protein.  It’s found normally in the body in very minute amounts, and it serves primarily as a response against viral infections, thus the name interferon. 

It was synthesized about 40 years ago in very, very small quantities.  Through the miracle of genetic engineering, it is now possible to synthesize this product outside the body so that it can be administered in relatively large quantities.

Interferon has a variety of activities, because it not only has effect in viral diseases, it probably confers some type of immunity to, also, bacterial diseases, and it’s been used in a large variety of cancers as well.

Andrew Schorr:                  

Okay.  Well, let’s talk about it as it relates to MPNs.  What has been the utility and the theory of how interferon can help with MPN?

Dr.  Silver:             

That’s an excellent question.  I introduced the use of interferon in the treatment of polycythemia vera about 25 years ago, and it was based upon the fact that interferon was effective in chronic myeloid leukemia. 

In fact, it was one of the first medicinal treatments, that's a medicine, that caused not only improved survival, but potentially long-term survival and near-cure, but only in unfortunately in a small number of patients who could tolerate large doses of interferon over a long period.

Now because polycythemia is one of the myeloproliferative diseases, and I was introduced into the myeloproliferative diseases by Dr.  William Dameshek when I was a young resident, who was the father of myeloproliferative diseases, as we all know, and I thought there was a great similarity among these diseases, in particularly PV and chronic myeloid leukemia.

I was very dissatisfied then, as I am now, in the use of hydroxyurea (Hydrea) because I think it has toxic potential. I think it can cause leukemia over the long-term use in a substantial number of patients, it can cause skin cancers, it has other toxicity on the liver and kidney, and so alternative forms of treatment are sought.

Now, interferon has a biologic basis for its use.  It affects stem cell division, it affects megakaryopoiesis.  Megakaryocytes are those giant cells in the bone marrow that cause platelet production, and platelets, as you know, are often elevated in patients with myeloproliferative diseases. 

It also can affect red cell cycling, so for all these reasons, I said, “My goodness, we should definitely try interferon.” In the first few patients that we reported in “The Lancet,” it had striking effect.

We expanded these trials and became the preferential use at Cornell.  Now, the important thing that must be stressed with interferon is that it must be used in low dose to begin with and the dose escalated.  It cannot be used over the long time in the same dose that patients were treated with chronic myeloid leukemia, because patients can't tolerate it.

For example, in the treatment of melanoma, interferon is given in a dose of 20 million units three times a week.  That's enormous.  Patients can't tolerate that, and so they stay in bed for a few years.  It’s a question of living or dying.

If you have that kind of option, then you stay in bed and tolerate the drug, but that's possible in patients with myeloproliferative diseases.  In contrast, we use tiny doses, 45 micrograms a week, so that’s a minuscule dose, and we can treat patients with that for long periods. 

Andrew Schorr:                  

My question is, where are we headed now with potential new products that can make interferon yet more useful?

Dr.  Silver:             

Again, that's a excellent question.  It’s very important to stress for our viewers that all the interferons are qualitative, meaning that it’s the same body of drug are the same.

There are several products commercially available, one made by Schering, that's interferon alfa-2b now, Schering-Merck.  There's another made by Roche, that's the Pegasys, and there's a new one now being manufactured by AOP and PharmaEssentia, which has a longer duration of activity.

If we can give a longer duration of activity with an injected drug instead of three times a week and make it once a month, that's extremely attractive to the patients.

Andrew Schorr:                  

Well tolerated.

Dr.  Silver:             

Well tolerated.  Now, the second thing is not only is it better tolerated, but the sustain level of interferon may allow for a better therapeutic effect, rather than the spike and dome effect that you see when you give the drug torrentially three times a week.

Andrew Schorr:                  

Okay.  Now, you mentioned the supplying to PV.  Might this also have any application in other MPNs, let’s say, myelofibrosis at all? 

Dr. Silver:              

Well, you’re asking a lot of questions.  I think we should tell the viewers this is unrehearsed. But you’re asking really excellent questions. Because we believe that this drug can also be effective, the interferon can be effective in early treatment of myelofibrosis. 

That's because in early phase myelofibrosis, the marrow retains cellularity and if we can decrease the fibrosis before the marrow becomes hardened with osteosclerosis, that that will be therapeutic advantageous. 

In fact, we published on the reversal of fibrosis in patients treated with interferon in a small series of cases, published in “Blood” in 2011, and now we've expanded the trial.  We have 32 patients on therapy for 10 or 15 years who have had a sustained response, 80 percent are in stable disease or improved, complete or partial remission.

Of course, my colleagues, who are skeptical, as we find at ASH, they say, “Well, that's a single-arm study,” but in diseases that are rare, and diseases of long duration, sometimes single-arm studies can, in fact, be efficacious.

Andrew Schorr:                  

Dr. Silver, just to sum up, you’ve been a proponent of interferon for many years, and you’ve explained why.  Do you feel that the engineering of the interferon now and the dose of the interferon, where we’re headed is it can be an increasingly useful tool in these categories of MPNs?

Dr. Silver:              

Absolutely.  I wanna stress that when I say this, I have no relationship with this company, and I've been introduced to the product.  I'm very enthusiastic about it because from a physician’s standpoint, I think there's added value to the way a long-acting interferon can serve the patient, both because of the practical administration once a month.

I think once a month, you have to make sure the patient takes it, because sometimes people have a tendency to forget them.  There's a basic physiologic reason whereby this can be of advantage because of the sustained levels of interferon for over a long period, namely a month rather than the spike and valley effect that we talked about.

Andrew Schorr:                  

Dr. Richard Silver, I wanna thank you for your devotion over decades… 

Dr. Silver:              

Well, thank you.

Andrew Schorr:                  

…to us with MPNs, really.  It’s a joy to meet somebody who’s really devoted their life to us, and as you hear, related to one component of the treatment array, if you will, interferon.  Engineering is going on to make effective products more useful, better tolerated for more people. 

Pay attention to that dialogue and see how it applies to you.  Have a dialogue with your doctor if you have PV, or as he said, myelofibrosis, that's sort of my situation, to see can that help us do better? 

On location at ASH with Dr. Richard Silver from New York City, I'm Andrew Schorr.  Remember, knowledge can be the best medicine of all.

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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Page last updated on December 18, 2015