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What is Selinexor (Xpovio) and Are There Side Effects?

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Published on September 8, 2020

Managing Side Effects of Selinexor (Xpovio) for Myeloma Patients

Selinexor (Xpovio) can have serious side effects but myeloma experts say it is less severe in smaller doses and in combination treatments. Watch Host and myeloma patient Cindy Chmielewski and Dr. Cesar Rodriguez of Wake Forest Wake Forest Baptist Health and Dr. Natalie S. Callander from the University of Wisconsin School of Medicine and Public Health discuss this new medicine for myeloma. They also discuss how other medications can be used to treat the side effects so patients can better tolerate this treatment option.

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Transcript | What is Selinexor (Xpovio) and Are There Side Effects?

What Should Myeloma Patients Know Before Taking Selinexor (Xpovio)?

Cindy Chmielewski: 

Let's move on to another drug that was probably approved within the last year selinexor (Xpovio). Now, that we've been using it more often I guess in the clinic, the side effects profile... are we able to manage that a little bit better? And maybe talk a little bit about selinexor in combination with other drugs, are we seeing a better side effects profile Dr. Callander? 

Dr. Callander: 

What a lot of people have learned just using selinexor commercially but specifically in these combinations is that one, that the higher doses of selinexor really do end up being I think problematic for patients. The lower doses actually people can tolerate much better and then they end up staying on the drug longer. I think that's a theme that you can see with other drugs that we use for myeloma treatments. So, some people tolerate the top doses of say lenalidomide (Revlimid) and pomalidomide (Pomalyst) very poorly, but once you cut the doses they can stay on them for a much longer time and get better benefit, so that's been my experience with selinexor. We've been very happy with the combination of selinexor with carfilzomib (Kyprolosand dexamethasone (Decadron), we've seen a lot of activity with that. There's a pretty good activity that's been presented... Well, very good actually with daratumumab (Darzalexin people who have not had daratumumab exposure.  

So I think probably the future of selinexor is that smaller doses will probably be combined with more agents, and there was just the BOSTON trial recently that came out combining selinexor with bortezomib (Velcade) which looked like they had very good response rates, and I believe that they will be going for that indication with Velcade very shortly. 

Dr. Rodriguez:

Then the most common side effects are GI symptoms mainly nausea, vomiting and decreased appetite. So we are doing a combination of several medications that help with nausea symptoms so Zofran or ondansetron with olanzapine, and we combine those two drugs with another drug called rolapitant and the dexamethasone. So the schema or the strategy that we've been doing is the day before somebody starts selinexor they start with Zofran and olanzapine and that way the Zofran's already in the system before they get their chemotherapy with selinexor. 

The day that they're getting the selinexor we give them the dexamethasone as a pre-med and we also give rolapitant as a pre-med, and then the olanzapine we continue on a daily basis after that and the Zofran which is used as needed. But by combining those medications we've seen the degree of nausea and vomiting and changes in appetite significantly be more manageable.  

In addition to that there's two other common side effects but they're not as common as nausea and vomiting, thrombocytopenia which is something that we're seeing with selinexor especially in people who have platelet count less than 150,000. It seems like the lower the platelet count at the time of the start is the higher the risk of having a drop in the platelets, and in order to manage that we either hold therapy and then adjust the dose so that... just like what we would do with lenalidomide or pomalidomide or any other chemotherapy that we're using for myeloma.  

Then hyponatremia is something that we don't normally see in other chemotherapies, but we're seeing in selinexor and about 18% of the cases. So what's causing the hyponatremia we're not sure if it's just the drug itself, or if it's the combination of the drug with the nausea and vomiting and not hydrating properly and having some diarrhea symptoms. So the way we manage the hyponatremia is by giving salt tablets and also doing hydration when they come to clinic if we see that their sodium level is on the low end. And by doing this the side effects that we were seeing with selinexor seem to be a bit more manageable, and patients can stay on treatment for a longer period of time. 

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