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Managing the Side Effects of Selinexor

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Published on February 28, 2020

Key Takeaways

  • Selinexor is approved by the FDA for the treatment of relapsed or refractory multiple myeloma in adult patients.
  • Giving a lower dose of selinexor and combining it with other agents can mitigate potential side effects.
  • If you have a diagnosis of multiple myeloma, consult a specialist for help and communicate any side effects that you experience during treatment.

The recent FDA approval of selinexor (Xpovio) for the treatment of relapsed or refractory multiple myeloma gives hope to patients who have already tried other therapies. This novel drug, however, is not without side effects.

Watch now as renowned expert Dr. James Berenson, Medical & Scientific Director at the Institute for Myeloma & Bone Cancer Research, explains the potential side effects of selinexor and how they can be managed. He also discusses the importance of patient-doctor communication.

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Transcript | Managing the Side Effects of Selinexor

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 in Southern California and near San Diego. A little further north in Los Angeles joins us a regular guest on Patient Power, and internationally known myeloma specialist, Dr. James Berenson. Dr. Berenson, welcome back to Patient Power.

Dr. Berenson:           

Thank you for having me.

Andrew Schorr:       

Sure. So, Dr. Berenson, we’ve been blessed with a raft of myeloma treatments over the last few years, including now for some of the sickest people. One of the drugs that was introduced months ago was a drug called selinexor (Xpovio) for people who had relapsed/refractory, had many other treatments, but yet, a drug like that and other drugs to have side effects. Where do we stand with managing the side effects so people wherever they are in their myeloma journey can have effective cancer treatment?

Dr. Berenson:           

Well, selinexor was recently approved as a single agent or approved with dexamethasone (Decadron) for heavily pretreated patients with five prior treatments including a couple of different proteasome inhibitors—drugs like carfilzomib, bortezomib, otherwise known as Kyprolis or Velcade, and also drugs such as an antibody like Darzalex or daratumumab, and then, immunomodulatory agents—drugs such as lenalidomide or pomalidomide, also known as Revlimid or Pomalyst. So, people failed a lot of these treatments and they were tried on this, and about 25 percent of people responded. Now, one can say that’s a really small percentage. But, if you look back at the older data leading to approval of pomalidomide, for example, with dexamethasone, similar percentage responded. And so, this is not really necessarily a bad thing, because it was used as a single agent. Of course, the problem is that the drug had a lot of side effects when it was given at the FDA-approved dose of 80 milligrams twice a week—a lot of nausea, vomiting, low blood counts, low appetite, anorexia, weight loss, even low sodium. So, these were major problems with the drugs.

So, there’s been an attempt to mitigate these with making sure that as soon as patients get on the drug, they get on things like ondansetron (Zofran), perhaps aprepitant (Emend). They also, some cases because of the poor appetite, get on olanzapine (Zyprexa). And for the sodium, they may require salt or fluid restriction, the mechanism that not really well done, well known or recognized why. And low blood counts, monitor carefully, may have to give them growth factors, platelets, et cetera. So, these patients need a lot of management. But, one of the other things I’ve learned over the years of doing myeloma for 35 years, you’re probably much better off giving less of something and combining it with something else and seeing that it’s active, but better tolerated. And so, that’s what’s happened with selinexor in combinations not yet approved, but in very promising trials combining it with immunomodulatory agents like pomalidomide. We’re starting a trial Revlimid—we’ve had good experience there—with Velcade, carfilzomib. So, this drug can be combined with other agents and quite nicely. And when you do that, you end up giving less drug. 

So, for example, instead of giving 160 milligrams or 80 milligrams twice a week, we’re only giving 60 mg once a week. We still see a fair bit of side effects. It’s certainly not the kind that we observed in the earlier trials of higher doses. And we certainly have to support these people with anti-nausea drugs and make sure we monitor their counts, make sure we check them for weight loss, their appetite, that sort of thing. So, there certainly can be a fair share of side effects. But, lowering the dose is very helpful. But, it’s also very helpful to encourage the patient, and we say this, that over time, these side effects go away. They get better. So, it’s usually a pretty big hump in road that these patients have the first month, but after that, things get better. And so, I think that although the drug has had a bad kind of reputation because of its tolerability, our experience has been as long as you follow closely these folks, watch them like a hawk and also encourage them, and also use lower dosage, you can get responses by combining it with other agents, to which the patient had been resistant to. So, these were not just responses because they would have happened, say, with a Revlimid or a Pomalyst. These people have failed all that stuff. So, I think I’m hopeful this drug may have play, but probably at lower doses.

Andrew Schorr:       

All right. Let me go over some of that with you. So, first of all, it involves communication with a myeloma specialist who is knowledgeable about the full range of drugs including selinexor so that you speak up about side effects, you’re monitored about side effects, and if there are trials or uses of drugs used in combination, that that can be explored for you. Did I get it right?

Dr. Berenson:           

Yeah, you got it all right. That’s right. Combining it with lower doses, better tolerability, making patients aware that things could be pretty rocky the first month, but after that, they can get a lot better. So, stick with it. Those are important. These are patients that have been really through the wringer. We’ve had patients who had 20 prior regimens getting responses—25-year history of myeloma. So, these are not newly diagnosed type patients who are getting this drug right now.

Andrew Schorr:       

Right. And I think where the FDA came in is, and where the research went in this drug is could there be yet another line of treatment and now learning, can it be used in combination with others to have more options for even the sickest people? And that is something to be commended. Now it’s learning best how to use it and how to help support people where it’s effective for them. 

Dr. Berenson:           

Yeah. And, it’s not just another chemo, or proteasome inhibitor, or an antibody or an immunomodulatory agent. It’s a whole new class of drugs we’re talking about, and it will probably lead to a lot of other analogs or versions, variations on the theme that hopefully will be better tolerated over the next few years.

Andrew Schorr:       

Okay. So, I think the message is for families dealing with this, whether you’re the patient yourself, been through so much or a loved one who’s trying to support them and really make sure that someone doesn’t suffer but gets the benefit of cancer fighting for every step of the way with myeloma. It’s a dialogue with someone like an expert like Dr. Berenson. How do we manage the side effects and still get the effectiveness of this medicine used alone or appropriately in combination so that we can continue the fight against myeloma, right, Dr. Berenson? 

Dr. Berenson:           

That’s correct. Now, also, I might chime in that there may be changes in the schedule of the drug may be helpful. So in that regards, for example, we are now studying a daily continuous dosing rather than the once or twice a week dosing, to see if low doses may be actually just as effective, at least in our animal models. Then we may do a trial if we see activity and better tolerability in the animals with a lower dose given more continuously than this intermittent higher dose. We’ll see.

Andrew Schorr:       

Okay. So, a whole new class of medicines, and experts and researchers like Dr. Berenson learning how best to use it to continue that fight against myeloma. We’re blessed with a range of treatments now including for the people who’ve been through so much. And we wish you and your family all the best for that. Dr. James Berenson from Los Angeles, thank you for all the work you do and thanks for helping people understand that the dialogue with their doctor about selinexor and managing side effects and maybe used in new ways, that’s so appropriate, that communication. Thanks for being with us, Dr. Berenson.

Dr. Berenson:           

Thank you. Thank you. 

Andrew Schorr:       

Andrew Schorr with Patient Power. 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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