Xpovio (selinexor)

What Is Xpovio (Selinexor)?

XPOVIO® (selinexor) is a “nuclear export inhibitor,” the first medication in this drug class to treat myeloma. Nuclear export inhibitors prevent cancer cells from expelling tumor suppressor proteins that help protect the cell from cancer. 

How Is Xpovio Used and Who Is a Candidate to Receive It?

Xpovio is used in multiple myeloma in both early relapse and late relapse settings. 

Xpovio was granted accelerated approval by the FDA for use in combination with the steroid dexamethasone [Xd] for the treatment of adult patients with relapsed and/or refractory myeloma who have received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody. The approval of the Xd regimen was based on data from Part 2 of the STORM phase IIb clinical trial.

In 2020, the FDA approved Xpovio in combination with Velcade® (bortezomib) and dexamethasone [XVd] for myeloma patients who have received at least1 prior therapy. The approval of the XVd regimen was based on data from the BOSTON phase III randomized clinical trial. Based on the FDA approvals,

Xpovio was initially used as part of the Xd protocol on a twice-weekly schedule (starting with a dose of 80 mg) or as part of the XVd protocol on a once-weekly schedule (starting with a dose of 100 mg). 

Xpovio in clinical practice in 2024 

Based on data from the STORM, BOSTON, and STOMP clinical trials with Xpovio, the National Comprehensive Cancer Network (NCCN) Guidelines for myeloma list the following treatment options:

Recommended for early relapse

• XVd once-weekly after 1–3 prior therapies.This combination is useful in certain circumstances (based on the STOMP clinical trial)
• Kyprolis® (carfilzomib) + Xd [XKd] once-weekly after 1 or more prior lines of treatment, with Xpovio dosing starting at 80 mg and Kyprolis dosing at 56 mg/m²
• Pomalyst® (pomalidomide) + Xd [XPd] once-weekly after 2 or more prior lines of treatment, with Xpovio dosing starting at 60 mg and Pomalyst dosing at 4 mg
• Darzalex® (daratumumab) + Xd [known as XDd, DXd, or Dara-Xd] once-weekly after 3 or more prior lines of treatment, with Xpovio dosing starting at 100 mg and Darzalex dosing at16 mg/kg. These combinations are for late relapse after 4 or more prior therapies.
• Xd twice-weekly, with Xpovio dosing starting at 80 mg. Your doctor may opt to start you on Xpovio at a dose as low as 40 mg, and may recommend one or more additional dose modifications.
   

How Is Xpovio Taken?

Xpovio is an oral (taken by mouth) medication in tablet form. Each tablet should be swallowed whole with water. Do not break, chew, crush, or divide the tablets. The recommended dose is 100 mg taken once weekly in combination with bortezomib and dexamethasone OR 80 mg taken orally on Days 1 and 3 of each week in combination with dexamethasone.

Your doctor will monitor your complete blood count (CBC), standard blood chemistry panel, and body weight before you start Xpovio and as needed during treatment.

Before and during treatment with Xpovio, you will receive treatment to prevent nausea and vomiting. Be sure to take your anti-nausea medication as a preventive before treatment with Xpovio, even if you’re not experiencing nausea. 

It is very important to maintain a good intake of food and fluids throughout your treatment with Xpovio.

Warnings and Precautions When Taking Xpovio

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.

Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony-stimulating factors.

Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.

Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.

Serious Infection: Monitor for infection and treat promptly.

Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.

Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract

Possible Side Effects of Xpovio

Side effects of Xpovio can be prevented or managed well with dose reductions, dose interruptions, or other supportive care. Common side effects include:

• nausea
• thrombocytopenia (low level of platelets)
• fatigue
• anemia (low level of red blood cells)
• decreased appetite
• diarrhea
• vomiting
• hyponatremia (low level of sodium in the blood)
• neutropenia (low level of neutrophils, a type of white blood cell)
• lymphopenia (low level of lymphocytes, a type of white blood cell)
• peripheral neuropathy
• hypophosphatemia (low level of phosphorus in the blood)
• decreased weight
• cataract
• constipation
• dyspnea (shortness of breath)
• upper respiratory tract infection

Support

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