A Lower Dose of Xpovio May Help Patients With Myeloma Get the ‘Full Benefit of the Drug’

Although patients with multiple myeloma may be concerned that a reduction in treatment dose may be less effective, an expert from The Tisch Cancer Institute stresses that it may be more beneficial.

Patients with multiple myeloma being treated with Xpovio (Selinexor), Velcade (bortezomib) and dexamethasone should discuss a decreased dosage of Xpovio if they are experiencing side effects from the drug. In fact, progression-free survival and duration of response were improved when patients reduced their dose appropriately, according to recent research.

In an interview with CURE®, Dr. Sundar Jagannath, Director of the Center of Excellence for Multiple Myeloma and a professor of medicine at The Tisch Cancer Institute in New York, discussed why these results are relevant for patients and how a dose reduction may improve outcomes.

CURE®: What are the key takeaways for patients with cancer that they should know about the findings?

Dr. Jagannath: What I presented was the outcome of patients who were treated with selinexor, bortezomib and dexamethasone versus bortezomib (plus) dexamethasone in a randomized clinical trial. This was called (the) BOSTON trial. This was an important trial, which resulted in full (Food and Administration) approval of selinexor for the treatment of multiple myeloma.

This was a phase 3 randomized international trial with a new drug, selinexor, in combination with bortezomib and dexamethasone. Whenever you're using a drug, especially a new drug, (that) is introduced into the market, people wonder about the potential side effects of the drug, and how to avoid the side effects in the patient.

And so in this particular trial, the selinexor dose could be modified according to the side effects that appeared in the patient, so you can reduce the dose. Everybody starts with selinexor once a week at 80 milligrams, bortezomib, also known as Velcade, once a week and dexamethasone once a week. And if there is any side effect to selinexor or Velcade or dexamethasone, you can reduce the dose. Then the question that comes is: if we reduce the dose, is it still effective? That becomes important.

What would you say to a patient who hears dose reduction and thinks that might mean they're getting less treatment and less benefit?

This drug is a unique mechanism of action, so it still works for these patients. It becomes an important drug, so we wanted to make sure this drug could be used safely in the patient. The advantage is that it is (an) oral medication, and it comes in tablets, 20 milligram tablets, so you can take four tablets to begin with once a week. You can cut it down to three tablets or increase it to five tablets. So dose adjustment becomes easier.

And this trial, we said that dose reduction starting at 80 milligrams but coming down to 60 milligrams or 40 milligrams, it was still effective. And that's the message important for the patient. Yes, if you experienced side effects, your doctors can adjust the dose and you will be able to tolerate it. And thereby you can get the full benefit of this drug.

How did you conduct your research?


We (looked at) the arm in which patients got selinexor, bortezomib and dexamethasone, (and identified) that 70% of them had dose reduction. And some of the patients didn't have dose reduction. And then we said, “was there a difference in the response rate, and how long they were in remission, on their outcome?”

What we were surprised to find (was) that the people who got dose reduced because of side effects, as well as the patients who didn't get dose reduced because they didn't experience side effects — there was not a big difference in terms of age of the patient, sex of the patient, or type of disease. So they were comparable.

So the next question that comes up is, OK, so at least they were comparable. So how did the patients who got dose reduced do as compared to patients who didn't have dose reduction? To our surprise, we found out that the patients who had dose reduction actually had a higher response rate, they had a response rate of 81.7%, as compared to 62%. And not only that, (but) the duration of the response was longer. So that outcome was better, the outcome measured in terms of progression-free survival, or overall survival. So it was actually that the progression-free survival improved to 17 months compared to nine months.

OK, so this is very important, that means you are able to manage the patient with this new drug in the combination to benefit the patient. You can adjust the dose of the drug, and because you adjust the dose of the drug, the efficacy doesn't go down. And because now it is tolerable, actually, the patients stay on the drug longer. And because they stay on the drug longer, they are able to control the disease much longer and more deeper responses are achieved. And therefore, the duration of response is better. The dose adjustment actually benefited the patient. So … yes, you can use this drug safely, you can dose reduce without worrying about efficacy going down. So that was the importance of this particular abstract.

You mentioned that the side effects were reduced. Can you talk more specifically about what were the most common side effects experienced and what patients might need to know?

Yeah, so there are two areas of side effects. One group of side effects, which is common when you use the chemotherapy drug, is lowering of the blood counts, (such as a) lower hemoglobin, lower white blood cell counts and lower platelet count. And this is not an uncommon side effect, it was also experienced in this combination with selinexor. And (to address) that you can adjust the dose and you can also use growth factors support, (such as) Neupogen, so that you are able to deliver that treatment.

Then the second set of side effects is what we call GI (gastrointestinal) side effects. (Since) this is a pill taken by mouth, so the patient could feel fullness, nausea, vomiting or diarrhea. (And) when you combine selinexor with bortezomib, which can also (cause) constipation or diarrhea known for Velcade (it can increase the amount of) side effects. And again, that could be mitigated by dose adjustment and giving nausea medication appropriately.

These were the two major side effects encountered with selinexor that could be handled. And if there are some uncommon side effects, that's where the dose reduction also helps with the patients.

Is there anything you wanted to add that we didn't touch upon?

The only thing I wanted to add is that this is an orally available treatment, so it is quite convenient, especially for people who have to travel to the infusion center some distances; that makes it easier. And if the elderly patients are dependent on family members having to take them to the cancer center, it becomes a lot easier.

There are orally available regimens because instead of Velcade, you can use it with Ninlaro. So you can have an all oral regimen — Ninlaro, selinexor and dexamethasone. So that's another option available.

This drug has no organ toxicity. It doesn't affect the heart, it doesn't affect the kidney, it doesn't affect the lungs, it doesn't affect the liver. So really this drug doesn't have any organ toxicity. And it could be combined with any other drug that has been (FDA) approved and is in the market for myeloma. So that is the other advantage of this particular drug.

This interview has been edited for conciseness and clarity.

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