Expert Outlook: New and Promising MPN Therapies in Clinical Trials

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Topics include: Treatment

Interested in learning more about developing options to treat myeloproliferative neoplasms (MPNs)? Treating MPNs isn’t a one-size-fits-all approach, and research done through clinical trials continues to expand the treatment arsenal. MPN experts Dr. Bart Scott of Seattle Cancer Care Alliance and Dr. David Snyder from City of Hope discuss potential new treatment options currently in development and clinical trials. Tune in to hear the latest.

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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. 

Beth Kart Probert:

Now I'd like to take the time to talk about some clinical trials. Dr. Scott, I'd like to have you start off with us. What’s new and promising? If you could talk about a few clinical trials that maybe are going on at SCCA, or that you’d like to share with us, and then, Dr. Snyder, we’ll go back to you. And you can give us your feedback. So, Dr. Scott, can you lead us into that subject?

Dr. Scott:              

Sure. We have a trial with a drug called imetelstat for patients with myelofibrosis. The accrual is currently on hold. A single center Phase II result was published in the New England Journal of Medicine showing there were some patients who were able to retain a remissionof their myelofibrosis with treatment with imetelstat.

This includes both molecular remission and morphologic remission. Molecular remission would mean that their abnormal mutations went away, and it responded, and morphologic remission would mean that visually the fibrosis had improved significantly. The Phase II trial is currently on hold, and they’re evaluating data. I’m helpful that the drug will continue to be explored in clinical settings. It does have a novel mechanism of action. It’s what’s called a telomerase inhibitor. 

As I said, the drug is known as imetelstat. There are many centers that were participating in that Phase II study. We just opened a trial with pacritinib. Pacritinib is also a JAK inhibitor, and actually I think it’s probably better to call these drugs JAK-STAT pathway inhibitors, because not all of them actually work directly on the JAK receptor, so I think that’s important to know.

These basically inhibit the JAK-STAT signaling cascade. This drug, pactritinib, is in clinical testing. It is not yet FDA approved. It’s somewhat similar to ruxolitinib (Jakafi), but it does appear to cause less cytopenias, so less toxicities with lowering of the blood count. It could be potentially useful in patients with low platelets. That’s one of the chief toxicities that can be seen with ruxolitinib are Jakafi is lowering of the platelet counts.

So I’m hoping that this drug will be approved in the near future. It was put on hold for the FDA for a brief period of time, but as I said the drug is now being studied again in a Phase II trial, looking at different dosings. There are many centers participating in that study.

And then we also have a transplant study that’s looking at giving JAK inhibitors before transplant in an effort to improve the overall condition of patients before they go into transplant. 

This is specifically for myelofibrosis patients. Patients with myelofibrosis can have a higher treatment-related mortality with transplantation because of other things that are going on with their body like malnutrition, the fact that they have a very big spleen, and other factors such as organ involvement with fibrosis can lead to a higher treatment-related mortality. They also have a slightly higher risk of graft failure in comparison to patients with other types of myeloid malignancies.

So we’re hopeful that giving a JAK inhibitor before transplant can help improve the post-transplant outcomes. So those are the three major trials that we currently have open. Of course, there are other centers with really exciting drugs in development, as well.

Beth Kart Probert:           

Wow, that sounds very exciting. I know that I can say just hearing that there’s such a focus with MPNs and these trials.

And, Dr. Snyder, what is going on in your neck of the woods at City of Hope and other trials that you’d like to tell us about? 

Dr. Snyder:           

Yes, we have a number of trials. We have the pacritinib and the imetelstat trial as well. We have two other trials that are for patients who have failed or progressed on ruxolitinib that have totally different mechanisms of action sort of outside of the pathways we’re talking about. One is called SL401, Stemline 401. It’s an interesting sort of an immuno-toxin; it’s a dual functional molecule that has an IL3, interleukin 3 portion that’s linked to a diphtheria toxin. It’s somewhat like a Trojan horse-type of thing. 

The cells in myelofibrosis and other hematological malignancies have an interleukin 3 receptor on their surface, and this IL3 molecule will bind to that interleukin receptor. That complex is taken inside the cells, and then the diphtheria toxin is released and is able to kill the cell from the inside. So that’s one mechanism. 

There’s another approach; there’s a molecule called CD47, which has been referred to as the “don’t eat me” signal. So, macrophages which are big cells in the body and in the blood and tissues, their name means big eaters. They like to eat foreign cells, tumor cells, bacteria, etc. 

 But some of the tumor cells or the malignancies become very clever, and they have this protein called CD47 on their surface that sends a signal to the macrophage: don’t eat me, stay away and helps the cells to survive. So there is an antibody against the CD47 that binds to the CD47 and interrupts that pathway and then allows the macrophages to do their jobs, which is to eat these abnormal cells.

So that’s another approach that’s being tested not just in myelofibrosis but in other conditions as well. There is some data, sort of preclinical, that this approach may actually reverse fibrosis in some models, so it’s kind of intriguing particularly for patients with myelofibrosis. 

The thing I will mention, we know that ruxolitinib is the only FDA-approved drug so far. There have been several others, unfortunately, that have gotten just so far and then because of toxicities have been taken off of the table. But to me, I think another approach is combination therapy that is taking ruxolitinib as the base and then combining it with the second drug that has a totally different mechanism of action, and the two of them then perhaps can synergize and kill off the cells. 

Those are trials, a quite a few of them going on around the country, and I think those have a lot of promise.

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 October 24, 2017