Yervoy

Approved Indications

Yervoy is an immunotherapy used to treat several types of advanced cancer. It is typically prescribed for cancers that are metastatic (have spread) or are unresectable (cannot be removed by surgery).

Melanoma

Yervoy is used to treat advanced melanoma in adults and children. It is also used as an adjuvant treatment to help prevent melanoma from returning after surgery in patients with cancer in their lymph nodes.

Combination Treatments

In many cases, Yervoy is used in combination with another immunotherapy drug called nivolumab. These combination uses include:

• Kidney Cancer: Advanced renal cell carcinoma that has not been treated previously.
• Colorectal Cancer: Metastatic colorectal cancer with specific genetic markers (MSI-H or dMMR) that has progressed after chemotherapy.
• Liver Cancer: Hepatocellular carcinoma in patients who were previously treated with sorafenib.
• Lung Cancer: Certain types of metastatic non-small cell lung cancer.
• Mesothelioma: Malignant pleural mesothelioma that cannot be surgically removed.
• Esophageal Cancer: Advanced or metastatic esophageal squamous cell carcinoma.

Mechanism of Action

Yervoy belongs to a class of drugs known as monoclonal antibodies. Specifically, it is a type of immunotherapy called a checkpoint inhibitor. It works by targeting a specific protein in the body called CTLA-4 (cytotoxic T-lymphocyte-associated protein 4).

The immune system uses checkpoints like CTLA-4 to keep immune responses in check and prevent the body from attacking its own healthy cells. However, some cancer cells can use these checkpoints to hide from the immune system.

Yervoy works by:

• Blocking the off switch: By binding to CTLA-4, the medication prevents this protein from sending a signal to turn off the immune response.
• Activating T-cells: Removing this brake allows T-cells, a type of white blood cell, to remain active and multiply.
• Targeting cancer: These activated T-cells are then better able to identify, reach, and destroy cancer cells throughout the body.

Because Yervoy stimulates the immune system generally, it may also cause the immune system to attack normal, healthy tissues in any part of the body.

Common Side Effects

• Fatigue
• Diarrhea
• Itching or skin rash
• Nausea and vomiting
• Headache
• Decreased appetite and weight loss
• Fever
• Insomnia
• Muscle, bone, or joint pain

Serious Side Effects

Yervoy works by stimulating the immune system, which can sometimes cause it to attack healthy tissues. These immune-mediated reactions can be severe or life-threatening and may occur during treatment or months after the last dose.

• Intestinal problems: Severe diarrhea, blood in stools, or severe stomach pain (colitis).
• Liver problems: Yellowing of the skin or eyes, dark urine, or pain on the right side of the stomach area.
• Hormone gland problems: Changes in mood or behavior, headaches, extreme fatigue, or weight changes affecting the pituitary, thyroid, or adrenal glands.
• Skin problems: Severe rash, itching, blistering, or peeling.
• Nerve problems: Weakness, tingling, or numbness in the hands or feet.
• Eye problems: Blurred vision, eye pain, or redness.

Infusion reactions can also occur during the administration of the medication. Patients should seek medical help immediately if they experience any new or worsening symptoms.

Immune-Mediated Adverse Reactions

Yervoy is associated with severe and sometimes fatal immune-mediated reactions. These occur when the medication causes the immune system to attack normal organs and tissues. These reactions can affect any part of the body, but most commonly involve the intestinal tract, liver, skin, nerves, and endocrine system.

• Digestive System: Severe inflammation of the colon (colitis) can lead to intestinal perforation. Symptoms may include diarrhea, blood in the stool, or severe abdominal pain.
• Liver: Immune-mediated hepatitis can cause liver failure. Monitoring of liver function tests is required before each dose.
• Skin: Serious skin reactions, including Stevens-Johnson syndrome or toxic epidermal necrolysis, have been reported.
• Endocrine System: Inflammation of the pituitary, adrenal, or thyroid glands can occur, requiring long-term hormone replacement therapy.
• Nervous System: Inflammation can lead to muscle weakness, numbness, or paralysis.

Monitoring and Management

Healthcare providers monitor for signs of these reactions through regular blood tests and physical exams. If severe reactions occur, treatment with Yervoy may be paused or permanently stopped, and high-dose corticosteroids may be prescribed to reduce the immune response.

Infusion Reactions

Severe infusion-related reactions can occur during the administration of the drug. Medical staff will monitor for symptoms such as fever, chills, shaking, itching, or dizziness during the infusion.

Pregnancy and Breastfeeding

Yervoy can cause harm to an unborn baby. Effective birth control is recommended during treatment and for several months after the final dose. It is not known if the medication passes into breast milk, so breastfeeding is generally not recommended during treatment.

Pregnancy

Yervoy can cause harm to an unborn baby. Research indicates that this medication may increase the risk of pregnancy loss or cause the immune system to attack the fetus. Patients should inform their healthcare provider if they are pregnant or planning to become pregnant before starting treatment.

Contraception

Individuals who can become pregnant are advised to use effective birth control during treatment with Yervoy. To ensure the medication has cleared the system, effective contraception should be continued for at least 3 months after the final dose. If a pregnancy occurs during treatment, it should be reported to a healthcare provider immediately.

Breastfeeding

It is not known if Yervoy passes into human breast milk. Because of the potential for serious adverse reactions in a nursing infant, breastfeeding is not recommended during treatment and for 3 months after the last dose.

Dosage Forms

Yervoy is supplied as a sterile liquid solution for intravenous administration. It is administered as an infusion into a vein by a healthcare professional.

• Intravenous solution

The medication is provided in vials and must be prepared and diluted by a medical provider before use.

FDA Approval History

Yervoy (ipilimumab) received its initial FDA approval in 2011 for the treatment of unresectable or metastatic melanoma. It was the first therapy shown to improve overall survival in patients with advanced melanoma. Over the following decade, its regulatory status expanded to include several other oncology indications, often in combination with other immunotherapies.

Approved Indications

The FDA has approved Yervoy for several specific uses, including:

• Melanoma: Treatment of unresectable or metastatic melanoma in adults and pediatric patients, and as adjuvant treatment for certain melanoma patients.
• Renal Cell Carcinoma: In combination with nivolumab for patients with intermediate or poor-risk, previously untreated advanced renal cell carcinoma.
• Colorectal Cancer: In combination with nivolumab for certain patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer.
• Hepatocellular Carcinoma: In combination with nivolumab for patients with liver cancer previously treated with sorafenib.
• Lung Cancer: In combination with nivolumab for certain types of metastatic non-small cell lung cancer.
• Pleural Mesothelioma: As a first-line treatment in combination with nivolumab for adults with unresectable malignant pleural mesothelioma.

Boxed Warning

The FDA requires a boxed warning for Yervoy due to the risk of severe and fatal immune-mediated adverse reactions. These reactions result from the drug's effect on the immune system, which can cause it to attack healthy tissues. Common sites for these reactions include the intestines (colitis), liver (hepatitis), skin (dermatitis), and endocrine glands (endocrinopathies). Early identification and management of these symptoms are critical for patient safety.

Estimated Pricing

Yervoy is a specialized biologic medication administered by intravenous infusion. The approximate cost for a 50 mg/10 mL vial is $8,411, while a 200 mg/40 mL vial is approximately $33,643. These prices are for the medication only and do not include additional costs for the infusion procedure, hospital fees, or laboratory monitoring.

Insurance Coverage

Most insurance plans, including Medicare and Medicaid, provide coverage for Yervoy when it is used for FDA-approved indications. Because it is administered in a doctor's office or clinic, it is usually processed through a patient's medical insurance rather than a prescription drug plan. Out-of-pocket costs like deductibles and coinsurance will vary by plan.

Financial Assistance

The manufacturer may offer support programs to help reduce costs for eligible patients. These options often include:

• Copay assistance for patients with private or commercial insurance.
• Patient assistance programs that provide the medication at no cost to those who meet specific financial and insurance criteria.

Generic Availability

There is currently no generic or biosimilar version of Yervoy available. It is only sold as a brand-name product.