MPN News From ASH 2016: Reviving the Role of Interferon Treatment

Published on

Topics include: Treatments and Understanding

As part of our 2016 ASH coverage, Dr. John Mascarenhas, from Mount Sinai School of Medicine, joined Patient Power to discuss the research taking place with interferon as a treatment for myeloproliferative neoplasms (MPNs). While interferon has been around for some time, there’s a recent re-emergence of research in the field. Dr. Mascarenhas addresses the interim results of current studies and the new clinical trials set to begin in 2017. Learn more about interferon and why this may be a viable option for some patients with MPNs.

 

View more programs featuring and

Transcript

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.  Well, when it comes to ET and PV and MPNs overall, including myelofibrosis, there's been so much talk about JAK inhibitors, but for years we've been talking for some of those conditions, particularly ET and PV, about the role of interferon. 

Well, with us is a leading expert who's been studying that, Dr. John Mascarenhas from Mount Sinai School of Medicine and an MPN cancer expert at the Tish Cancer Institute in New York City.  Thank you so much for being with us. 

Dr. Mascarenhas:

Thanks for having me.  

Andrew Schorr:

So let's talk about interferon. 

Dr. Mascarenhas:

Okay. 

Andrew Schorr:

We've had it for a long time.  There have been—you know sometimes it's been tough to take for people, but we've been trying to make it easier and see what its role is.  Where are we now? 

Dr. Mascarenhas:

So interferon is an interesting drug.  It's a drug that's not new and is not an oral drug.  It's not a novel therapy in the way that we talk about it in a lot of these meetings, but it is an active drug in many different diseases but particularly in MPNs, and we've known that for quite some time.  The difficulty often has been how to deliver it safely and effectively without reducing the quality of life of a patient. 

So we know from laboratory studies that have been done that the drug works at the level of the hematopoietic stem cell, and we're always talking about how we want to target that malignant hematopoietic stem cell to quiet it down and allow for normal hematopoiesis, normal blood cell development.  Well, peginterferon alfa-2a (Pegasys) is a drug that we think has that capability, and that again stems from scientific study, but also in Phase II studies of Pegasys in patients with ET and PV that have been done both in Europe and the U.S. over the years have shown a signal of clinical activity.  So a lot of things look good in the lab but don't necessarily translate nicely and the clinic. 

Well, Pegasys is one of those drugs that does seem to have activity, not necessarily in every patient, but has response rates in terms of normalizing the blood counts and reducing the spleen in the majority of patients that are treated.  Now, what it seems to do, which is very sort of enticing and exciting compared to therapies previously, is actually modify the disease in a way that may be more profound that simply reducing blood counts.  

So, for example, measuring the mutation level, the burden or the amount of that driver mutation in your blood like the JAK2 V617F, we use that as a surrogate marker for how well we're treating someone with this disease.  There's debate on whether that's a great marker for it, but it's the marker that we have.  And in studies with Pegasys, namely, that drug induces complete molecular remission, so removing the ability to detect that by a technique called PCR in 15 to 20, 25 percent of patients, and that's where sort of the excitement has been. 

And over the last five-plus years there's really been a concerted effort by many investigators to formally evaluate Pegasys, and specifically I think one of the most important studies is the MPD?RC 112 study.  And that's a consortium study that we have, and the MPD-RC is an NCI-sponsored consortium.  It's a group of very dedicated laboratory and clinical investigators that have come together to—to really shift the way we treat these diseases into a more effective therapies.  And with 43 sites around the world, it's a very potent group of investigators. 

The hypothesis was that the pegylated interferon, Pegasus, would be superior to hydroxyurea in inducing complete hematologic remissions in patients with high-risk ET and PV.  So these are patients that are at risk—when we say high-risk at risk for what, risk for having clots or risk for having progression to myelofibrosis or risk for having MPN-related death.  So these are patients that were in need of treatment, and they were randomized one to one to hydroxyurea (Hydrea) versus Pegasys.  

Hydroxyurea has been around for a long time.  It's an effective drug in reducing hematologic remissions.  There's been a concern for quite some time revolving around the potential for leukemogenicities, so the potential for it to induce or accelerate leukemic transformation, and that's a real concern that has patients and physicians worried.  

Andrew Schorr:

To become an AML.  

Dr. Mascarenhas:

To become an AML.  You don't want to become an AML, and God forbid a physician gave you a drug that accelerated that.  That would be horrific, so there's always been this concern.  Thankfully, no retrospective study or prospective study to date has actually really shown that to be true. 

This was a study that was geared to showing that there was an advantage of one over the other.  So patients were randomized, a total of 168 patients in the case of the MPD-RC 112 study, randomized, to receive either hydroxyurea, which is an oral agent, or Pegasys, which is a subcutaneous agent, and both have very different mechanisms of action. 

And the readout is at 12 months of therapy, that's the primary readout, which arm has a better response rate.  Is it the hydroxyurea arm, or is it the Pegasys arm.  Now, the patients are treated beyond that, and there are other end points that we're looking at, but that was really the primarily end point of the study. 

The study is written—most studies, particularly big studies like this, are written with an interim analysis, meaning that after you enroll a certain number of patients, and they've had a certain period of time in order to be valuable. You pause and you—you look to make sure that there is no signal of clear activity of one that would then make it then not ethical to continue a study or that there's a clear signal of toxicity or bad outcomes in one that would then make it not ethical to continue the study.   

So we didn't see that with the interim analysis, and at this meeting we'll present the interim analysis of the MPD-RC 112 study in which the response rates, the hematologic response rates at 12 months in the two arms in 75 patients that were randomized and intention to treat analysis were the same and that there really wasn't a difference in outcome as measured by ELN criteria, so a set criteria of normalizing the counts, reducing the spleen and reducing the symptom burden. 

What's also interesting from this study—and I will stress again for the patients listening to this, these are interim results, these are preliminary results.  We need to wait for the full, mature results to really make conclusions that will be paradigm shifting and treatment shifting.  But what was also interesting and sort of unexpected is that if you look at the hydroxyurea arm there were, in fact, both bone marrow pathologic responses and complete molecular remissions in that arm, and I think that surprised many of the investigators involved in the study. 

And I should point out I'm fortunate enough to be talking about it, but it's really off the backs of many people who participated.  So beyond all of the brave patients that participated in a randomized study, there are—I don't know even know how many, but I can tell you multiple investigators both in the U.S., Canada, Israel, UK, Germany, Italy and France that participated. 

This was a global study.  This was really a tremendous effort by a group of dedicated individuals, and it goes way beyond the investigators, data management personal, statisticians, a whole group of people that really put their best foot forward to create a trial that would give us prospective data in which physicians around the world can base their treatment rather than opinion. 

Andrew Schorr:

Okay.  So interferon versus hydroxyurea. 

Dr. Mascarenhas:

So far at an early time point, at one year, all I can say is there's no difference.  We really—it's one of those we got to wait and see what the rest of the study shows.  There will be many investigators and scientists that will say, well, John, at one year that's an early time point.  The real effects of interferon will take longer, and that's very valid.  I totally agree with that, that at one year, although the two may look equivalent, that at two years, three years we may really see that the benefit in Pegasys has outweighed and that hydroxyurea is not equivalent. 

So we really have to wait, but at least—at this very interim part of the study I can say with confidence that if you take hydroxyurea you are not at risk, more risk of having a bad outcome.  In fact, it's probably the same outcome as taking Pegasys. 

Andrew Schorr:

Okay.  So the role the interferon and—as far as people having a supply of interferon to go forward, and now you have some new players coming in.  And I know there's something called the RESCUE study.  Where does this fit in?  

Dr. Mascarenhas:

So, unfortunately, the MPD-RC 112 study which is the—the MPD-RC is an NCI-sponsored consortium, but the study, the drug itself and some of the funding for the study was graciously given to us by Roche.  And, unfortunately, that supply now is going to end, and the study therefore will end in June of next year, and that poses some dilemma because…=

Andrew Schorr:

…June of 2017. 

Dr. Mascarenhas:

June of 2017.  And I should point out there's a sister study called the MPD-RC 111, which is a salvage study of Pegasys in patients who are already intolerant or refractory to hydroxyurea, and that has about 135 patients that were enrolled in that study.  That study also has concluded—will conclude this month, in fact, and drug supply will not be available through the company. 

Andrew Schorr:

December of 2016. 

Dr. Mascarenhas:

December 2016.  So this poses a problem because this leaves a number of patients enrolled in these studies without the guarantee of getting the Pegasys that they were receiving.  And this is unfortunate, because these are drugs that are typically taken over a prolonged period of time and not necessarily short intervals. 

We have been in discussions with a company called PharmaEssentia Corporation, which is a Taiwanese?based company.  They have a very interesting drug.  Many of your patient viewers may even be aware of it, called Ropeginterferon.  It's an interferon alfa-2B with a novel PEGylation formulation, and therefore it's a longer acting Pegasys—interferon.  It's dosed less frequently, and perhaps the toxicity profile is better than Pegasys.  Whether it's more efficacious we don't know,

And the reason why I'm bringing up this agent is we are in the middle of embarking on a new trial called the RESCUE trial, R-E-S-C-U-E.  I can't remember the exact name of the full trial, but it spells out rescue if you look at it.  If you go to clinicaltrials.gov you won't find it yet because it's not yet approved.  It's a drug—it's a trial that's already being developed.  Actually at this meeting today all of the investigators are getting together with the company. 

We're finalizing how we're going to move forward with this, but this will be a trial that will be hopefully available, I'm hoping the second quarter of 2017 for patients specifically that were on the MPD-RC 111 and 112 patients that didn't have excessive toxicity with Pegasys and are interested in rolling over to another trial that will give them access to this newer formulation of interferon alfa.  

Andrew Schorr:

Okay.  So interferon, we're still trying to figure out its role and continuing studies and then in this case maybe an additional supply of a new formulation where patients can continue.  

Dr. Mascarenhas:

Yep. 

Andrew Schorr:

Okay.  So interferon is still a useful tool?  

Dr. Mascarenhas:

I think so.  I think it's like most drugs in this field.  I think it's a useful tool but in a specific subgroup of patients.  Our goal, or one of the goals of the trial, of the MPD-RC 11 and 112, one of the goals of what's called the PROUD-PV study, which is a study of the Ropeginterferon in high?risk ET or PV patients that are hydroxyurea resistant or intolerant, that will be also presented at this meeting, is to really define and be able to elucidate perhaps which subgroup of patients really garner the benefit from this type of therapy. 

Because it's probably not one drug fits all, and perhaps for older patients where the toxicity may be more, and perhaps the benefit may be less obvious, maybe it's not for those patients.  Perhaps it's for younger patients, earlier on in their disease course.  Perhaps it can control the momentum of the disease in a very important way, so we have to figure it out. 

We have to look at, for example, things that we've talked about in a former session, the mutational or molecular profile of patients.  Perhaps there's a signature that will tell us which patients are more likely to benefit, because it really doesn't make sense to give even patient one drug when it's likely that a fraction of those patients will really benefit from it, and perhaps the other patients should be treated with something else. 

Andrew Schorr:

Okay.  Dr. John Mascarenhas from Mount Sinai, thank you so much for being with us and the research you continue to help lead with colleagues, peers around the world.  

Dr. Mascarenhas:

Thanks for having me. 

Andrew Schorr:

We're very grateful.  I think the message for patients when it comes to interferon is, of course, check in with an MPN specialist related to this and the research that's ongoing to see is there a trial that matches up with your situation.  Does interferon have a role for you? 

Thank you for being with us.  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. 

Related Programs

How Can I Combat Depression Associated With Interferon Therapy?

Patient Power community member, Kathy, asks Dr. John Mascarenhas about the connection between depression and interferon therapy and how the condition can be managed.

Published:

Advertisement
Join Our Community Register for Events Read Our Latest Blog
Advertisement

Page last updated on August 9, 2017