Xpovio (selinexor)

What Is Xpovio (Selinexor)?

XPOVIO® (selinexor) is the first and only medication in the drug class known as selective inhibitor of nuclear export (SINE) that has been approved to treat myeloma by the FDA. Xpovio works by preventing myeloma cells from expelling tumor suppressor proteins that help protect the cells from cancer, thereby interfering with myeloma cell growth.

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. 

FDA approval of Xpovio

In 2019, 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 or refractory multiple myeloma (RRMM) 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. This FDA approval was based on data from Part 2 of the STORM phase 2b clinical trial, and Xpovio was initially given on a twice-weekly schedule (starting with a dose of 80 mg).

In 2020, the FDA approved Xpovio in combination with Velcade® (bortezomib) plus dexamethasone (XVd) for myeloma patients who have received at least 1 prior therapy. This FDA approval was based on data from the BOSTON phase 3 randomized clinical trial, and Xpovio was initially given on a once-weekly schedule (starting with a dose of 100 mg).

Xpovio in NCCN Guidelines

The National Comprehensive Cancer Network (NCCN) Guidelines list additional treatment options based on the STORM, BOSTON, and STOMP studies: 

• For early relapse (after 1–3 prior therapies), XVd once-weekly.
• Useful in certain circumstances (based on the STOMP clinical trial)
  • After 1 or more prior lines of therapy, proteasome inhibitor Kyprolis® (carfilzomib) plus Xd (XKd) once-weekly with Xpovio dosing starting at 80 mg.
  • After 2 or more prior lines of therapy, immunomodulatory agent Pomalyst® (pomalidomide) plus Xd (XPd) once-weekly with Xpovio dosing starting at 60 mg.
  • After 3 or more prior lines of therapy, either the intravenous (IV) Darzalex® (daratumumab) or the subcutaneous (SQ) Darzalex Faspro® (daratumumab plus hyaluronidase-fihj) monoclonal antibody plus Xd (known as XDd, DXd, or Dara-Xd) once-weekly with Xpovio dosing starting at 100 mg.
• 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 a medication taken by mouth in the form of a tablet. Swallow the tablet whole with water. Do not break, chew, crush, or divide the tablets. Each Xpovio tablet should be taken at approximately the same time of day. 

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

Your doctor will prescribe medication for nausea and vomiting to be taken before and during treatment with Xpovio. You must take this medication as prescribed by your doctor, even if you’re not experiencing any nausea or vomiting. If you have any questions or concerns about your prescribed medication, discuss this with your doctor. 

Throughout your treatment with Xpovio, it is very important to maintain good intake of food and fluids. If necessary, you may receive IV fluids to prevent or treat dehydration

Warnings and Precautions When Taking Xpovio

Neurological toxicity

In the BOSTON clinical trial, 26% of patients with myeloma who received Xpovio 100 mg once weekly experienced neurological adverse reactions (excluding peripheral neuropathy) that included dizziness, fainting, depressed level of consciousness, vertigo, amnesia, and mental status changes (including delirium and confusion). Severe Grade 3 or Grade 4 events occurred in 3.6% of patients. The median time to the first event was 29 days. Discontinuation due to neurological adverse reactions occurred in 2.1% of patients.

In the STORM clinical trial, 30% of patients with myeloma who received Xpovio 80 mg twice weekly experienced neurological adverse reactions, including dizziness, fainting, depressed level of consciousness, and mental status changes (including delirium and confusion). Severe events (Grade 3–4) occurred in 9% of patients. The median time to the first eventwas 15 days.

Cataracts

In the BOSTON clinical trial, the incidence of new onset of or worsening cataracts requiring clinical intervention was reported in 22% of patients with myeloma during treatment with Xpovio 100 mg. The median time to new onset of cataracts was 228 days and was 237 days for worsening of cataracts in patients presenting with cataracts at start of Xpovio therapy. Treatment of cataracts usually requires surgical removal of the cataract.

Embryo-fetal toxicity

Xpovio can cause fetal harm, based on its mechanism of action as well as on data from animal studies. Females of reproductive potential and males with a female partner of reproductive potential must use effective contraception during treatment with Xpovio and for 1 week after the last dose. Do not use Xpovio if you are pregnant. Contact your doctor promptly if you become pregnant or if pregnancy is suspected during treatment with Xpovio.

Lactation

There is no information about the presence of Xpovio in human milk, or its effects on the breastfed child or milk production. Because of the potential for serious adverse reactions in a breastfed child, women should not breastfeed during treatment with Xpovio and for 1 week after the last dose.

Infertility

Based on findings in animals, Xpovio may harm fertility in males and females of reproductive potential.

Possible Side Effects of Xpovio

Good communication with your doctor is extremely important while you are receiving treatment for myeloma. If you experience any side effects, alert your doctor as soon as possible. Your side effects may be managed with supportive care, dose reductions, or dose interruptions. It is always better to deal with a problem immediately than to let it get worse.

In the STORM phase IIb clinical trial of Xd, side effects that occurred in 20% or more of the study patients were thrombocytopenia, fatigue, nausea, anemia, decreased appetite, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

In the BOSTON phase III clinical trial of XVd, the most frequent Grade 3 or Grade 4 side effects were thrombocytopenia (39% in the XVd group vs. 17% in the Vd group), fatigue (13% vs.1%), anemia (16% vs. 10%), and pneumonia (11% in both study arms).

Thrombocytopenia

Thrombocytopenia is a low number of platelets in the blood. Platelets help blood to clot; fewer platelets can lead to easier bruising, bleeding, and slower healing. The “normal” level varies from laboratory to laboratory. For example, at Mayo Clinic the “normal” level is ≥ 150,000 platelets per microliter of circulating blood. If the platelet count is less than 50,000, bleeding problems could occur. Major bleeding is usually associated with a reduction to less than 10,000. Xpovio may cause thrombocytopenia.

Prevention and treatment of thrombocytopenia

Your doctor will monitor your platelet counts at baseline and during treatment, especially during the first two months. Management of low platelet counts may include interruption, reduction, or permanent discontinuation of your dose of Xpovio; platelet transfusions; or medication to stimulate the production of platelets.

Nausea or vomiting

In the STORM phase IIb clinical trial, 72% of the 202 study participants experienced nausea (9% of the cases were severe), and the median time to the onset of the first episode of nausea was 3 days after starting Xpovio. Vomiting was reported in 41% of patients (4% of the cases were severe), and the median time to onset of first vomiting was 5 days after starting Xpovio.

Prevention and treatment of nausea and vomiting

Your doctor will prescribe a required anti-nausea medication along with your prescription for Xpovio. Even if you’re not experiencing nausea, it is very important to start taking your anti-nausea medication as a preventive prior to treatment with Xpovio. Continue taking the anti-nausea medication as directed during treatment with Xpovio, even if you are not experiencing nausea. Your doctor may also manage your nausea by delaying, reducing, or stopping your treatment with Xpovio, and may also administer IV fluids to replace electrolytes and prevent dehydration.

Fatigue

Fatigue is commonly associated with cancer and with cancer therapy. Fatigue that is related to cancer and its treatments is different from and more severe than normal fatigue, tends to last longer, and includes the feeling of overall weakness (the medical term for this is asthenia).

For more information about this debilitating side effect, read the IMF’s publication Understanding Fatigue in Myeloma.

Prevention and treatment of fatigue

Let your medical team know if you are experiencing fatigue. Your doctor may prescribe a medication to help minimize your fatigue. The effects of fatigue may also be minimized by maintaining the following:

• A moderate level of activity.
• A healthy diet and proper fluid intake.
• A consistent sleeping schedule.
• Regularly scheduled visits with your doctor to monitor your red blood cell count (low red blood cells, or anemia, can cause fatigue) and to discuss issues that may be contributing to your fatigue.
• A careful review of the side effects of any other medications you are taking to ensure that they are not contributing to your fatigue.

Anemia

Red blood cells contain hemoglobin, a protein that carries oxygen to the body’s tissues and organs. Anemia is usually defined as a decrease in hemoglobin < 10 g/dL or as a decrease of ≥ 2 g/dL from the normal level for an individual. More than 13–14 g/dL is considered normal. Low levels of oxygen in the body may cause shortness of breath and feelings of exhaustion.

Prevention and treatment of anemia

Your doctor will determine which treatment regimen for anemia is best suited to and safest for you. Treatment of anemia may include the following:

• Interruption, reduction, or discontinuation of your dose of Xpovio
• Blood transfusions
• Erythropoietic (red blood cell-making) medication

Decreased appetite

In the STORM phase IIb clinical trial, 53% of the study participants experienced decreased appetite (5% of the cases were severe).

Prevention and treatment of decreased appetite

Your doctor will give you a prescription for anti-nausea medication to help prevent loss of appetite and may also manage this side effect by interrupting and/or modifying the dose and schedule of Xpovio. You may be asked to weigh yourself daily and report the results to your doctor in order to monitor your condition closely.

A publication by the National Cancer Institute (NCI), Eating Hints: Before, during, and after Cancer Treatment, may offer helpful suggestions.

Diarrhea

Diarrhea is defined as 3 or more loose stools per day. Severe diarrhea is defined as 7 or more loose stools per day, requiring treatment with IV fluids or hospitalization.

Prevention and treatment of diarrhea

Your doctor will modify your dose of Xpovio and/or use standard antidiarrheal medications such as Imodium® (loperamide HCl) to help control diarrhea. Dizziness, light-headedness, or fainting may occur due to dehydration caused by excessive or persistent diarrhea. If you become dehydrated, your doctor may order IV fluids for you.

Hyponatremia

Sodium is an electrolyte, one of the minerals in the blood and other body fluids that carries an electrical charge and is essential for life. Sodium helps to regulate the amount of water that is in and around the cells, nerve and muscle function (including the heart), and other important body processes. Vomiting and diarrhea can lead to reduced concentrations of sodium in the blood.

Prevention and treatment of hyponatremia

Your doctor will monitor your levels of sodium before and during the first two months of your treatment with Xpovio. Your doctor will review your diet and may treat you with an IV saline solution or with salt tablets, or might make other recommendations. Your dose of Xpovio may be interrupted, reduced, or discontinued depending upon the severity of the hyponatremia.

Neutropenia

Neutropenia is a reduced level of neutrophils, a type of white blood cell necessary in fighting bacterial infections. Having too few neutrophils can lead to infection. Fever is the most common sign of neutropenia. If you have a fever, you must get immediate medical attention. Fever caused by neutropenia is called febrile neutropenia.

Prevention and treatment of neutropenia

Your doctor will assess your baseline neutrophil count before you start treatment with Xpovio. You will be monitored closely during the first two months of treatment, including for signs and symptoms of infection. Contact your doctor immediately if you have a fever, and make sure you have an emergency or after-hours number to reach a doctor if yours is not available. You may be given antimicrobial therapy if you are showing signs of infection. Your doctor may also prescribe a granulocyte colony-stimulating factor (CSF) to increase production of your white blood cells. Your dose of Xpovio may be interrupted, reduced, or discontinued based on the severity of your neutropenia.

Constipation

The medical definition of constipation is 3 or fewer bowel movements in one week. The stool may be hard, dry, and difficult to pass. You may also have stomach cramps and bloating. Not eating, not drinking enough water, and being less active can contribute to this problem.

Prevention and treatment of constipation

• Report your constipation to your doctor.
• Drink sufficient fluids.
• Try to eat high-fiber foods.
• Try to be active every day, even if you exercise in a chair. Moving your body increases the rhythmic contractions that move food through your intestines.

Infections

In the STORM phase IIb clinical trial, 52% of study participants experienced an infection. Upper respiratory tract infection occurred in 21% of the patients, pneumonia in 13%, and sepsis, the body’s potentially life-threatening response to an infection, occurred in 6% of patients. Severe infections were reported in 25% of patients, and deaths resulting from an infection occurred in 4% of patients. Most infections were not associated with a low neutrophil count. Tell your doctor immediately if you have any signs and symptoms of infection, including:

• Fever
• Flu-like symptoms (body aches, sweating, chills)
• Sore throat
• Cough (which may produce phlegm)
• Shortness of breath
• Chest pain when you breathe or cough

Prevention and treatment of infections

You must report your symptoms to your doctor, who will determine how the symptoms should be managed and if you need to receive an antibiotic or other medications. If your doctor or another doctor covering the practice is not available, you should go to an urgent care or emergency facility

Xpovio in Clinical Trials

Learn more about clinical trial options across the U.S. by using the IMF's Clinical Trials Matching Engine powered by SparkCures.

The U.S. government maintains the website clinicaltrials.gov, an online database of thousands of research studies from around the world. You may wish to also explore this resource. However, the U.S. government does not review or approve the safety and science of all the studies listed on this website.

For more information about what’s involved in study participation, read the IMF’s publication Understanding Clinical Trials in Myeloma.

Support

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