Managing Myeloma Side Effects with Xpovio (Selinexor)

Selinexor, also called Xpovio®, is the first drug in the class known as XPO1 inhibitors. It has been approved for many years in myeloma, initially as a single agent (given with dexamethasone) and now in combination with several other myeloma drugs. 

We have learned over the years that every drug in myeloma goes through an evolution. By that, I mean that after a drug is approved, we become more comfortable using it. Inevitably, the exact dosing of the drug changes, and we often develop methods to make giving the drug easier. The goal here is twofold: We want to make it more effective, but we also want to reduce side effects. 

We have seen this happen with literally every drug we use in myeloma. For example, Velcade® has gone from twice weekly to mostly once weekly, and it has gone from being given IV (intravenous) to now in the skin (subcutaneous). Kyprolis®, which was initially given twice weekly, is now given once weekly. Darzalex® was previously given intravenously, and now it is mostly given subcutaneously. Also, with Darzalex, we have adjusted the pre-medications to ensure side effects are lessened.  

Now, we have seen a similar evolution with Selinexor. So, in this video, I want to provide practical tips as to how we currently give this drug to maximize its benefits and minimize its side effects. This is particularly important because when it was first introduced, Selinexor caused several side effects like nausea, anorexia (not wanting to eat), low blood counts, and fatigue. As a result, many were afraid to use it or even dismissed it. Now, it is being used with a different approach and more extensively. 

Today, I would suggest the following 5 steps be taken to best reduce the risk of side effects with Selinexor: 

1. Choose the right starting dose. 
2. Use the drug weekly. 
3. Always start with 2 antinauseant drugs. 
4. Ensure good communication between the patient and the healthcare team. 
5. Remember the first month is the worst month. 

Choose the right starting dose. 

When we first started using Selinexor, we gave it 80mg twice weekly for a total of 160 mg per week. We have learned now that a much lower dose is as effective and much better tolerated. As a result, I start patients at somewhere between 40mg and 80mg once weekly, along with dexamethasone and whatever other partner drug is being given such as Velcade®, Kyprolis®, Pomalyst®, or Darzalex®. 

Use the drug weekly. 

As noted above, we have reduced the dose of Selinexor, and we give it only once weekly. The BOSTON trial validated this use, in which it was given once weekly along with once weekly Velcade. This dosage and scheduling are simpler and cause fewer side effects, such as nausea, for patients. 

Always start with 2 antinauseants. 

We also validated this strategy in clinical trials to PREVENT nausea and anorexia, and not only react to it. I suggest using what we call a 5HT3 antagonist (usually a drug like ondansetron – also known as Zofran) to reduce nausea. I give it “continuously,” or every 8-12 hours, the day before; the day of; and the day after the Selinexor pill is taken. I also do the same with Olanzapine (Zyprexa) by giving it the night before, the night of, and the night after the Selinexor pill to reduce anorexia. I give these additional drugs for at least the first month and then taper them down. 

Ensure good communication between the patient and the healthcare team. 

This, of course, is ALWAYS important in the care of myeloma patients, but particularly so when using Selinexor. I discuss the potential for nausea with my patients and their partners, so they are prepared for it. Then, we keep in close communication to ensure things are going well, and we adjust if we need to.  

Remember the first month is the worst month. 

In my experience, if we can manage the side effects in the first month, it is considerably better thereafter. As the body adjusts to this new drug, it tends to be much easier for patients. We can often reduce the amount of antinauseants, too. 

Selinexor is an important part of the treatment approach that we have in multiple myeloma. We want to ensure we optimize its use so patients can have the maximum benefit. I hope this video and strategy will help providers, patients, and their partners as they use this drug.