Xpovio

Multiple Myeloma

Xpovio is used to treat adults with multiple myeloma, a type of plasma cell cancer. It is prescribed in the following situations:

• In combination with bortezomib and dexamethasone: For patients who have received at least one prior therapy for their cancer.
• In combination with dexamethasone: For patients with relapsed or refractory multiple myeloma who have already tried at least four other types of treatment, and whose cancer did not respond to specific therapies including proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies.

Diffuse Large B-cell Lymphoma (DLBCL)

Xpovio is also used to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) that has returned (relapsed) or did not respond to treatment (refractory). This includes DLBCL that started from follicular lymphoma. It is typically used after a patient has received at least two other types of systemic cancer treatments.

Mechanism of Action

Xpovio belongs to a class of medications known as selective inhibitors of nuclear export (SINE). It works by blocking a specific protein in the body called exportin 1 (XPO1).

In a healthy cell, XPO1 helps transport various proteins from the nucleus (the center of the cell) to the cytoplasm (the outer part of the cell). However, in many types of cancer, XPO1 is overactive and moves tumor suppressor proteins out of the nucleus too quickly. These tumor suppressor proteins are necessary to identify damaged cells and prevent them from multiplying uncontrollably.

By blocking XPO1, Xpovio keeps these tumor suppressor proteins trapped inside the nucleus. Once they accumulate in the nucleus, they can perform their job of:

• Identifying and repairing damaged DNA.
• Stopping the cancer cell from dividing and growing.
• Triggering a process called apoptosis, which is the programmed death of the cancer cell.

Because cancer cells often rely more heavily on XPO1 than healthy cells do, Xpovio is designed to target the cancer cells while having a different effect on normal, healthy cells.

Common Side Effects

Many people taking Xpovio experience digestive issues or fatigue. Common side effects may include:

• Nausea and vomiting
• Diarrhea or constipation
• Loss of appetite and weight loss
• Feeling very tired or weak
• Shortness of breath
• Changes in the way food tastes
• Blurred vision

Serious Side Effects

Some side effects can be serious and may require immediate medical care. Contact your doctor if you experience:

• Low blood cell counts: This includes low platelets (increased bruising or bleeding), low red blood cells (anemia), and low white blood cells (increased risk of infection).
• Neurological problems: Confusion, dizziness, fainting, or changes in mental status.
• Low sodium levels: Symptoms may include headache, confusion, or feeling weak.
• Severe dehydration: Often caused by persistent nausea, vomiting, or diarrhea.
• Vision changes: New or worsening cataracts or blurred vision.

Your healthcare provider will perform regular blood tests to monitor your blood counts and electrolyte levels while you are taking this medication.

Blood Cell Count Reductions

Xpovio can cause a significant decrease in blood cell counts, which may be severe or life-threatening. Healthcare providers typically monitor blood counts at the start of treatment and frequently thereafter.

• Thrombocytopenia: Low platelet counts can increase the risk of serious bleeding.
• Neutropenia: A decrease in white blood cells can make it harder for the body to fight infections.
• Anemia: Low red blood cell counts may cause fatigue and weakness.

Gastrointestinal Toxicity

Nausea, vomiting, diarrhea, and loss of appetite are very common. These symptoms can lead to severe dehydration and weight loss. Patients are often prescribed anti-nausea medications before and during treatment to help manage these effects.

Neurological Effects

This medication may cause neurological issues such as confusion, dizziness, fainting, or decreased alertness. Because of these risks, caution is advised when driving or operating machinery until the effects of the drug are known.

Sodium Levels

Low sodium levels in the blood (hyponatremia) can occur during treatment. This condition may be severe and often requires monitoring of blood chemistry and potential dietary or medical adjustments.

Infection Risk

There is an increased risk of developing serious infections, including pneumonia and sepsis, while taking Xpovio. Any signs of infection, such as fever or chills, should be reported to a healthcare provider immediately.

Cataracts

New or worsening cataracts have been reported in patients taking this medication. Vision changes should be monitored by an eye specialist if they occur.

Pregnancy and Reproduction

Xpovio can cause harm to a developing fetus. Effective contraception should be used by both females and males with female partners of reproductive potential during treatment and for a specified time after the final dose. Breastfeeding is not recommended during treatment.

Pregnancy

Based on its mechanism of action and findings from animal studies, Xpovio can cause fetal harm when administered to a pregnant woman. There are no adequate studies of Xpovio use in pregnant humans to determine a drug-associated risk of birth defects or miscarriage. In animal studies, the medication caused embryo-fetal death and structural abnormalities at doses lower than the recommended human dose.

Healthcare providers typically verify the pregnancy status of individuals who can become pregnant before starting treatment. Because of the potential risks, the following precautions are generally recommended:

• Females of reproductive potential: Use effective contraception during treatment and for one week after the final dose.
• Males with female partners of reproductive potential: Use effective contraception during treatment and for one week after the final dose.

If you become pregnant or think you may be pregnant while taking this medication, notify your healthcare provider immediately.

Breastfeeding

It is not known whether Xpovio passes into human breast milk or if it affects milk production or the breastfed child. Because of the potential for serious adverse reactions in a nursing infant, it is advised that individuals do not breastfeed during treatment with Xpovio and for one week after the last dose.

Available Forms

Xpovio is available as a film-coated tablet for oral administration. The medication is typically supplied in blister packs designed to facilitate specific treatment cycles.

• Oral tablet

FDA Approval History

Xpovio, which contains the active ingredient selinexor, was first granted accelerated approval by the U.S. Food and Drug Administration (FDA) in July 2019. Initial approval was based on response rates in patients with heavily pretreated multiple myeloma. Subsequent approvals expanded its use for other indications based on further clinical data.

Approved Indications

The FDA has approved Xpovio for the following uses in adults:

• Multiple Myeloma: Used in combination with bortezomib and dexamethasone for patients who have received at least one prior therapy. It is also approved for use with dexamethasone alone in patients who have received at least four prior therapies and whose cancer is resistant to several other classes of treatment.
• Diffuse Large B-cell Lymphoma (DLBCL): Used as a single agent for patients with relapsed or refractory DLBCL, including cases arising from follicular lymphoma, after at least two lines of systemic therapy.

Regulatory Requirements and Monitoring

Xpovio is available only by prescription. While it does not have a Boxed Warning, the FDA requires specific monitoring during treatment due to the risk of serious side effects. Healthcare providers must monitor blood counts, liver function, and nutritional status regularly. Because some indications were approved under the accelerated approval pathway, continued approval for those uses may depend on the results of ongoing confirmatory trials.

Factors Influencing Cost

Several variables determine the final price of Xpovio:

• Insurance Coverage: Your out-of-pocket costs will depend on your specific health insurance plan, including your deductible, co-pay, or co-insurance requirements.
• Dosage and Frequency: Xpovio is available in various strengths and dosing schedules. The total cost may change based on the number of tablets required for each cycle of treatment.
• Pharmacy Type: This medication is often distributed through specialty pharmacies, which handle complex medications that require special storage or monitoring.

Generic Availability

Xpovio is a brand-name medication containing the active ingredient selinexor. There is currently no generic version available. Generic drugs usually cost less than brand-name versions because they do not require the same initial research and development investment.

Financial Assistance Programs

Patients who are prescribed Xpovio may have access to financial support options. These can include:

• Manufacturer co-pay cards for patients with commercial insurance.
• Patient assistance programs for those who are uninsured or underinsured.
• Support from independent charitable foundations that help cover the cost of oncology medications.