Using XPOVIO (selinexor) and Velcade weekly with low-dose dexamethasone showed a 47% increase in progression free survival compared to Velcade (twice weekly) and low-dose dex, according to updated results from the Phase III BOSTON study.

Today, XPOVIO is FDA approved to be used with dexamethasone only after four prior lines of therapy and Karypharm is looking to broaden the FDA’s approval of the drug in multiple myeloma care.

The study (involving 402 patients) was interesting as it used a weekly dose of Velcade and a weekly dose of XPOVIO. Typically, Velcade is given twice weekly. Using both drugs on a weekly basis could lower the overall side effect profile of both drugs for myeloma patients. Using the drugs together may provide an opportunity to also lower the dose of both drugs which could also lower side effects while maintaining effective use against myeloma.

Median progression-free survival was 13.93 in the selinexor/Velcade/dex (SVd) arm compared to 9.46 in the Velcade/dex (Vd) arm. There were no new major side effect concerns when adding Velcade to the XPOVIO/dex combination. 

Importantly, the study included myeloma patients who had 1-3 prior lines of therapy which represents earlier use of XPOVIO. (The current FDA approval is for 4 prior lines of therapy).

Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm said:  

“In the study, patients on the SVd regimen lived 47% longer without their disease worsening, which we believe represents an important improvement in the treatment of patients with relapsed or refractory multiple myeloma.  We also intend to submit these data as quickly as possible to the U.S. Food and Drug Administration (FDA) as part of a supplemental New Drug Application seeking to expand the approved indication for XPOVIO into second line treatment for patients with relapsed or refractory multiple myeloma. If approved, the SVd regimen would be the first and only FDA-approved combination drug regimen that includes once-weekly Velcade therapy for relapsed myeloma.”

The greatest side effect of Velcade is neuropathy. Early side effect management is critical for patients on XPOVIO. Because it is a new drug, many providers don’t yet know how to best manage the side effects, but myeloma doctors are learning they can borrow experience from their peers who treat solid tumor cancers whose patients experience similar side effects. Here are some tips for managing the side effects of XPOVIO. You should always involve your doctor in managing your side effects. Speak up and let them know what you are experiencing and the severity so they can lower your dose or change your treatment accordingly. 

Thrombocytopenia (low platelet count)

• Monitor platelet counts at baseline and  during treatment, especially in the first two months of therapy. 
• Watch for bleeding issues. 
• Patients can receive platelet infusions. 
• Interrupt and/or reduce the dose (or discontinue) if this is severe 

Neutropenia (low white blood cell count)

• Watch neutrophil counts at baseline and  during treatment, especially in the first two months of therapy. 
• Watch for infections. 
• Consider using antibiotics or antifungals to prevent infections
• Consider using growth factors (G-CSF)
• Interrupt and/or reduce the dose (or discontinue) if this is severe 

Gastrointestinal Issues

• Use anti-nausea medications before and during treatment
• Give IV fluids and replace electrolytes if nausea/vomiting is an issue to prevent dehydration
• Interrupt and/or reduce the dose (or discontinue) if this is severe 
• Manage diarrhea by dose modifications and/or standard anti-diarrheal agents; administer intravenous fluids to prevent dehydration in patients at risk.
• Patients’ weight should be monitored if they don’t feel like eating on XPOVIO
• Modify the dose or take nutritional support or appetite stimulants if you don’t feel like eating. 
• Interrupt and/or reduce the dose (or discontinue) if this is severe 

Low Sodium

• Watch sodium levels at baseline and  during treatment, especially in the first two months of therapy. 
• Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Use IV with salt or salt tablets. 
• Interrupt and/or reduce the dose (or discontinue) if this is severe 

Neurological Issues

• Optimize hydration status, hemoglobin level, and associated medications to avoid marking dizziness or mental status worse. 

Infections

• Consider using antibiotics or antifungals to prevent infections