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New Clinical Trial for Myelofibrosis Patients with JAK2 Mutation

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Published on November 5, 2020

Trial Utilizes New Drug for Treatment of JAK2 Mutation Positive Myelofibrosis

An exciting new clinical trial is exploring the use of selinexor (Xpovio) for JAK2 mutation positive myelofibrosis patients who either have difficulty tolerating ruxolitinib (Jakafi), or for whom Jakafi is no longer effective. Early results are showing promising results.

Dr. Srinivas Tantravahi from the Huntsman Cancer Institute, University of Utah joins Patient Power Co-Founder and myelofibrosis patient, Andrew Schorr, to discuss the origins of this trial, the first set of patient results and what Dr. Tantravahi is hoping to accomplish. We also meet Doug Ahmer, the fourth patient to join the clinical trial, to learn what brought him to the trial and what his early results have shown.

For more information about this trial, visit or call 1-888-424-2100.

This program is sponsored by Karyopharm Therapeutics. This organization has no editorial control, and Patient Power is solely responsible for program content.


Transcript | New Clinical Trial for Myelofibrosis Patients with JAK2 Mutation

What is Primary Myelofibrosis?

Andrew Schorr: Hello, and welcome to Patient Power. I'm Andrew Schorr in Southern California, joining us from the Huntsman Cancer Institute in Utah is physician and clinical investigator, Dr. Srinivas Tantravahi. Doctor, there's research going on at Huntsman and I'm very interested because it's been about myelofibrosis and I have primary myelofibrosis. I've been on JAK inhibitors, but I understand they don't work for everybody or they don't continue to work for everybody.

Myelofibrosis is a more advanced form of myeloproliferative neoplasms (MPNs). Myelofibrosis typically causes symptoms including a very large spleen and quality of life issues with night sweats, weight loss, and fatigue. About 60% of primary myelofibrosis patients carry a JAK2 mutation.

What are JAK Inhibitors?

Dr. Tantravahi: Thank you, Andrew. We’ve made some advances in terms of treating myelofibrosis and that is development of these drugs called JAK inhibitors. We have now two different JAK inhibitors, but the most common drug that's used is something called ruxolitinib also called as Jakafi in the United States.

And this drug can be quite effective, particularly in decreasing the size of the spleen and also improving the quality of life. We haven't shown that this treatment actually can modify the disease biology very much. There is increased sort of trend for better survival in this patient population, but it doesn't necessarily cure the disease or modify the disease to a large extent. Ironically, the drug can make anemia and thrombocytopenia, which are actually very common in myelofibrosis patients, much worse. A lot of patients cannot tolerate the required dose because of anemia or low platelet counts.

Andrew Schorr: Eager to find a solution for patients who could not tolerate the available JAK inhibitors, Dr. Tantravahi and colleagues at Huntsman Cancer Institute discovered the protein that was critical to the survival of myelofibrosis cancer cells in the lab.

What is Selinexor (Xpovio)?

Dr. Tantravahi: And it turns out that there's also a drug that inhibits this specific protein and that protein is called XPO1 and the drug was selinexor (Xpovio). And at the time selinexor was in clinical trials for many different malignancies, particularly the forefront of all of those was multiple myeloma. So, when we saw these results, it was really exciting because we've thought this particular protein was essential for these cells. And we also came to know that there's actually a drug that can inhibit that. So, we decided to test that drug.

Andrew Schorr: So, you all were studying myelofibrosis, trying to understand the genes that were fueling the malignancy if you will, recognizing that the JAK inhibitors maybe dealt with symptom management, but maybe didn't knock out the cancer.

Dr. Tantravahi: That's right. Yeah.

Andrew Schorr: So, you noticed a gene and lo and behold, there was a medicine that targets that gene.

Dr. Tantravahi: Absolutely. Yep.

Andrew Schorr: Selinexor. You applied for funding and there you go. And you have a phase two trial for patients to carry forward and try to fight the underlying condition, particularly patients who haven't benefited or benefited enough from a JAK inhibitor.

Dr. Tantravahi: That's right.

Andrew Schorr: How's it going?

How Effective is Selinexor in Treating MF?

Dr. Tantravahi: The study is going pretty good. So far, we have enrolled 10 patients on the study. What we observed so far is that the disease improves certain blood parameters like such as white blood cell count. Often MF patients have a high white blood cell count. So even after the one dose of selinexor, we've noticed a trend of white blood cell count coming down. Typically, after about 12 weeks of treatment, we are observing a decrease in spleen, both by our clinical exam and also by MRI scans. In terms of the drug potentially eradicating the MF cells, we need more time.

Andrew Schorr: The study is currently open and being conducted at the Huntsman Cancer Institute at the University of Utah in Salt Lake City.

 So, Doctor, your trial is open. A phase two trial. Who is a candidate to be in this trial?

Who is a Candidate for the Clinical Trial?

Dr. Tantravahi: That's an excellent question. So, the study is essentially designed for two categories of patients. One is those patients that are having difficulties in tolerating, either ruxolitinib or other JAK inhibitors because of either low blood counts or any other specific side effects. And the second is for patients who have already been treated with ruxolitinib, either it stopped working over time or it hasn't decreased the spleen size as expected. In both situations, many people have a hard time tolerating the drug or the drug is no longer working, would be eligible to participate in our study.

What Type of Medicine is Selinexor?

Andrew Schorr: So, selinexor is an oral medicine. So, while there's monitoring that you have to do in scans, they're taking pills.

Dr. Tantravahi: That's absolutely right. This is not an infusion medicine. It is an oral medicine and it's also taken once a week. That's very much more convenient that patients do not need to travel for infusions to the hospitals or the cancer center where they're getting treatment. But instead, most of the treatment is done at home. There are monthly follow-up visits, but the treatment itself is an oral medicine that's taken by mouth once a week.

Are There Side Effects to This Drug?

Andrew Schorr: The side effects observed in the clinical trial who take a weekly dose of selinexor are decrease in appetite, weight loss, and nausea, and fatigue. Participants in the study are encouraged to take an appetite stimulant and meet with a nutritional counselor.

Doctor, what are you hoping for that will come out of this trial?

What are the Goals of the Clinical Trial?

Dr. Tantravahi: At the moment, stem cell transplant is the only procedure that has the potential to cure this disease, but that has several limitations, including availability of donor and also many other complications that come with such a high-risk procedure. There's no question that JAK inhibitors have changed the natural course of this disease to a large extent, but we still have some unmet need, particularly when these drugs cause too many side effects or no longer be effective. So, my hope is that this drug provides an option beyond the JAK inhibitors for patients with myelofibrosis and also improve their quality of life and potentially make this disease a chronic illness that they can live with, with a better quality of life.

Andrew Schorr: This is an important area of research for those of us who are living with myelofibrosis. Can there be new mechanisms of action, new kinds of medicines that could come into play? And I want to thank you. And the folks who work with you at the Huntsman Cancer Institute for pushing this forward. We'll be following this trial. And I'm sure there are people who are watching who may want to contact you to be in it. Thank you for being with us.

Dr. Tantravahi: Thank you so much for having me. I'm happy to be contacted by anybody if they're interested in the study or have any more questions related to either the study or the disease of myelofibrosis itself.

Andrew Schorr: Let’s hear from a patient who's in the clinical trial.

Clinical Trial Patient Story

Doug Ahmer: My name is Douglas Ahmer and I was diagnosed with myelofibrosis in May of 2016.

In 2017, Doug began taking Jakafi for treatment of his myelofibrosis.

 From the time I got my diagnosis I just naturally began doing a lot of reading, and one day there was an article from the Salt Lake Tribune that showed up that showed Dr. Tantravahi and his group at Huntsman and they announced that they had a study that had just started.

November 2019, Doug was the fourth myelofibrosis patient to join the study with Dr. Tantravahi.

My spleen had started growing and that was the primary indicator that Jakafi was losing its effectiveness. I'd been on Jakafi for about a year and a half. When we started off the trial and they baselined me my spleen was about seven times normal and this last May, which was at the 24-week mark, we had a scan done and my spleen had reduced in size by 70%.

So, I've seen a great reduction and that all means that my disease is being controlled. That the progression in the disease has been slowed, if not stopped. And so, I'm just extremely happy with the test results that I've seen coming out of this drug trial with selinexor.

The primary side effect Doug has encountered has been loss of appetite. He is currently taking an appetite suppressant that does help, but he has lost considerable weight.

I want to continue on this drug. I mean, it's controlled my disease. I can't say that I'm being cured or I'm in remission or heading to remission. I'm the number four person in Dr. T's trial – they're still trying to figure those kinds of things out.

Why did you decide to participate in a clinical trial?

It just seems that there are so many drugs that are out there in development right now with some really good ideas behind them. I'm trying to stay healthy enough that when something comes along, either a combination or an individual drug or something comes along that actually could be marketed as a cure that would put the disease into remission. I want to be alive to be able to take advantage of that.

Doug and his wife are currently traveling the Southwestern United States.

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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