What to Know About Yervoy (Ipilimumab)

Yervoy (ipilimumab) is an immunotherapy drug approved to treat a variety of cancers, including melanoma, kidney cancer, colon cancer, liver cancer, and certain types of lung cancer. It is administered through your vein and may be given alone or in combination with another immunotherapy drug called Optivo (nivolumab).

The goal of Yervoy (and other immunotherapies) is to prompt your immune system to attack cancer cells within your body. Yervoy does this by targeting and inhibiting a protein receptor called cytotoxic T lymphocyte-associated protein 4 (CTLA-4).

This protein receptor normally acts as an immune checkpoint and decreases the function of T cells within your immune system. By blocking CTLA-4, Yervoy can increase T cell recognition and destruction of cancer cells.

While generally well-tolerated, Yervoy may cause a person's immune system to misguidedly attack their own tissues and organs. These immune-related toxicities need to be carefully monitored during treatment. Depending on their severity, withholding Yervoy or discontinuing it may be warranted.

Uses

Yervoy is approved by the Food and Drug Administration (FDA) for the treatment of the following cancers:

Melanoma

Yervoy is approved to treat melanoma in adults and children who are 12 years and older whose cancer cannot be removed by surgery (unresectable) or has spread to other parts of the body (metastasized).

Yervoy is also approved as an adjunctive (additional) treatment in patients who have undergone complete resection (removal of the cancer), including total lymphadenectomy (lymph node removal).

Renal Cell (Kidney) Cancer

Yervoy is approved to treat—in combination with Opdivo (nivolumab)—patients with intermediate or poor-risk, previously untreated, advanced renal cell carcinoma.

Colorectal Cancer

Yervoy is approved to treat (in combination with Opdivo) adults and children (12 years of age and older) with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, Eloxatin (oxaliplatin), and Camptosar (irinotecan).

Hepatocellular (Liver) Cancer

Yervoy is approved to treat hepatocellular carcinoma (in combination with Opdivo) in patients who have been previously treated with Nexavar (sorafenib).

Non-Small Cell Lung Cancer

Yervoy is approved as a first-line treatment (in combination with Opdivo) of metastatic non-small cell lung cancer in adults whose tumors express the PD-L1 protein but not any mutations in the epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genes.

Yervoy is also approved as a first-line treatment (in combination with Opdivo and platinum chemotherapy) of metastatic or recurrent non-small cell lung cancer in adults whose tumors express no EGFR or ALK mutations.

Pleural Mesothelioma

Yervoy is approved as a first-line treatment (in combination with Opdivo) of unresectable malignant pleural mesothelioma in adults.

Before Taking

Before taking Yervoy, it's important to tell your healthcare provider all of the medications you are taking, including prescription and over-the-counter drugs, herbal supplements, and vitamins.

Also, tell your healthcare provider about any health conditions you have, including:

• Autoimmune diseases (e.g., ulcerative colitis, Crohn's disease, Addison's disease, thyroid disease, systemic lupus erythematosus (SLE), or sarcoidosis)
• Organ transplant
• Liver disease

Tell your healthcare provider too if you are pregnant, breastfeeding, or planning on becoming pregnant or breastfeeding.

Contraindications

There are no contraindications listed in the manufacturer's (Bristol-Myers Squibb Company) labeling for Yervoy.

Precautions

There are some precautions to consider with your healthcare provider before taking Yervoy.

Pregnancy

Yervoy can harm an unborn baby. Before starting treatment, a pregnancy test should be done on anyone capable of becoming pregnant. Additionally, if applicable, people capable of becoming pregnant who take Yervoy should be on some form of birth control during treatment and for three months after their last dose.

If you were to become pregnant on Yervoy, tell your healthcare provider right away. You and your healthcare provider should immediately contact the manufacturer, Bristol-Myers Squibb. You may be encouraged to participate in a Pregnancy Safety Surveillance Study.

Breastfeeding

Since it's unknown whether Yervoy passes into breast milk, you should not breastfeed when taking Yervoy and for three months after the last Yervoy dose.

Stem Cell Transplantation

Patients receiving Yervoy either before or after an allogeneic stem cell transplant (when stem cells are taken from a donor) may develop fatal or serious graft-versus-host disease. The benefits versus risks of taking Yervoy after an allogeneic stem cell transplant need to be carefully weighed.

Age 75 and Older

Patients age 75 or older with non-small cell lung cancer or malignant pleural mesothelioma have been found to experience a higher rate of drug discontinuation due to adverse reactions. Be sure to speak with your healthcare provider if you fall into this category.

Other Immunotherapy Drugs

Alternative immunotherapy drugs used to treat some or all of the cancers that Yervoy treats include:

• Opdivo (nivolumab)
• Keytruda (pembrolizumab)
• Tecentriq (atezolizumab)
• Imfinzi (durvalumab)
• Bavencio (avelumab)

Dosage

Yervoy is given by intravenous infusion (generally over 30 to 90 minutes) and may be given either alone or in combination with Opdivo. The specific dose depends on its indication for treatment.

The dosage strengths, according to the manufacturer, are as follows:

• Unresectable or metastatic melanoma: 3 milligrams Yervoy per kilogram body weight (mg/kg) every 3 weeks for a total of 4 doses
• Adjuvant treatment of melanoma: 10 mg/kg every 3 weeks for 4 doses, followed by 10 mg/kg every 12 weeks for up to 3 years
• Advanced renal cell carcinoma: 1 mg/kg every 3 weeks for 4 doses (in combination with Opdivo), followed by additional Opdivo doses
• Microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer: 1 mg/kg every 3 weeks for 4 doses (in combination with Opdivo), followed by Opdivo alone
• Hepatocellular cancer: 3 mg/kg once every 3 weeks (in combination with Opdivo) for 4 combination doses, followed by Opdivo alone
• Metastatic, PD-L1 expressing non-small cell lung cancer IV: 1 mg/kg once every 6 weeks (in combination with Opdivo)
• Metastatic or recurrent non-small cell lung cancer: 1 mg/kg once every 6 weeks (in combination with Opdivo and 2 cycles of platinum chemotherapy)
• Unresectable malignant pleural mesothelioma: 1 mg/kg once every 6 weeks (in combination with Opdivo) for up to 2 years

The number of doses you receive depends on factors like whether the cancer is progressing or whether any toxicity develops. Before and during treatment with Yervoy, you will have multiple appointments with your healthcare provider and can expect to undergo various blood and imaging tests.

Modifications

There are no dosage adjustments listed in the manufacturer's labeling for patients with kidney or liver impairment.

How to Take and Store

Yervoy is administered by a healthcare provider at a hospital, an infusion center, or your oncologist's office.

Yervoy should be stored in a refrigerator at a temperature of 36 F to 46 F (2 C to 8 C) and kept in its original carton until its time of use to protect it from light. Yervoy should not be frozen or shaken.

Side Effects

The most common side effects associated with Yervoy include:

• Tiredness
• Diarrhea
• Itching
• Rash
• Colitis (inflammation of the colon)

When Yervoy is taken in combination with Opdivo, additional side effects include:

• Muscle, bone, and joint pain
• Cough
• Fever
• Decreased appetite
• Nausea, vomiting, and abdominal pain
• Headache
• Shortness of breath
• Dizziness
• Low thyroid hormone levels (hypothyroidism)
• Decreased weight

When Yervoy is taken in combination with Opdivo and platinum chemotherapy, additional side effects include:

• Pain in muscles, bones, and joints
• Nausea
• Decreased appetite
• Constipation

When Yervoy is taken at the higher 10 mg/kg dose (used sometimes to treat melanoma), additional side effects include:

• Nausea
• Vomiting
• Headache
• Weight loss
• Fever
• Decreased appetite
• Insomnia

Warnings and Interactions

Yervoy can lead to the development of severe, even fatal, immune-related adverse reactions that affect the intestines, liver, skin, hormone glands, lungs, kidneys, nervous system, heart, eyes, and/or the musculoskeletal system.

These reactions may occur because Yervoy increases the function of T cells, which may erroneously attack a person's own body instead of the cancer. These reactions usually occur during treatment with Yervoy; however, they may also develop after treatment.

Identifying these reactions early and managing them immediately (usually with corticosteroids to suppress the immune system) is critical. In some cases, if the reaction is severe, the patient may need to withhold or permanently stop Yervoy.

When taking Yervoy, please contact your healthcare provider right away if you develop any of the following signs or symptoms:

• Intestinal signs/symptoms: Diarrhea, mucus or blood in your stools, black sticky stools, and/or abdominal pain
• Liver signs/symptoms: Jaundice, dark-colored urine, nausea or vomiting, pain on the upper right side of your stomach, and/or abnormal bleeding or bruising
• Skin signs/symptoms: Rash with or without itching, sores in your mouth, blistering or peeling skin
• Endocrine (hormone) signs/symptoms: Persistent or unusual headaches, abnormal tiredness, feeling cold all the time, weight gain or weight loss, mood or behavior changes, dizziness or fainting, increased appetite or thirst, and/or urinating more often than usual
• Lung signs/symptoms: New or worsening cough, chest pain, and/or trouble breathing
• Kidney signs/symptoms: Decreased urine production, blood in your urine, swelling in your ankles, and/or decreased appetite
• Brain and nerve signs/symptoms: Unusual weakness of legs, arms, or face, headache, fever, fatigue or weakness, confusion, memory problems, hallucinations, seizures, and/or stiff neck
• Heart signs/symptoms: Shortness of breath, irregular heartbeat, fatigue, and/or chest pain
• Eye signs/symptoms: Blurry or double vision, eye pain, and/or eye redness
• Muscle and joint signs/symptoms: Severe or persistent muscle or joint pains and/or severe muscle weakness

Graft-versus-host disease may occur in patients who receive Yervoy before or after an allogeneic stem cell transplant. Potential signs and symptoms of this complication include rash, nausea, jaundice, abdominal pain, and diarrhea.

Infusion reactions may also occur when taking Yervoy. If the reaction is mild or moderate, the rate of infusion may be stopped temporarily or slowed. The drug should be discontinued for severe and life-threatening reactions.

Drug Interactions

Yervoy, in combination with Zelboraf (vemurafenib) for treating melanoma, may improve the response rate. There may, however, be an increased risk for developing liver toxicity. If taken together, your oncologist will carefully monitor you with regular liver function blood tests.