YERVOY (Ipilimumab)
Immune Checkpoint Inhibitor — Anti-CTLA-4 Monoclonal Antibody for Cancer Immunotherapy
Quick Facts About YERVOY
Key Takeaways About YERVOY
- Immune checkpoint inhibitor: YERVOY blocks CTLA-4, boosting the immune system's ability to fight cancer cells
- Multiple cancer indications: Approved for melanoma, renal cell carcinoma, NSCLC, mesothelioma, colorectal cancer, esophageal cancer, and hepatocellular carcinoma
- Often combined with nivolumab: Most indications use YERVOY together with OPDIVO (nivolumab) for enhanced efficacy
- Immune-mediated side effects: Can cause serious inflammation in any organ — report symptoms immediately to your oncologist
- Hospital administration only: Given as a 30-minute IV infusion under specialist supervision, not a take-home medication
What Is YERVOY and What Is It Used For?
YERVOY (ipilimumab) is a cancer immunotherapy drug that contains the active substance ipilimumab, a fully human monoclonal antibody. It works by blocking CTLA-4, a molecule that normally puts a brake on your immune system, thereby allowing your T-cells to more effectively recognize and destroy cancer cells.
Ipilimumab belongs to a class of drugs known as immune checkpoint inhibitors. The immune system has natural checkpoints that prevent it from attacking normal, healthy cells. Cancer cells can exploit these checkpoints to avoid being destroyed. YERVOY targets one such checkpoint called CTLA-4 (cytotoxic T-lymphocyte-associated antigen 4). By blocking CTLA-4, ipilimumab amplifies the activation and proliferation of T-cells, including those capable of infiltrating and destroying tumors.
YERVOY was the first immune checkpoint inhibitor approved for cancer treatment and represented a breakthrough in oncology. It was initially approved by the U.S. Food and Drug Administration (FDA) in 2011 for the treatment of unresectable or metastatic melanoma, and subsequently by the European Medicines Agency (EMA). Since then, its approved indications have expanded considerably.
Approved Indications
Ipilimumab is approved for the following cancer types, either as monotherapy or in combination with other treatments:
As monotherapy (YERVOY alone):
- Advanced melanoma (unresectable or metastatic) in adults and adolescents aged 12 years and older
In combination with nivolumab (OPDIVO):
- Advanced melanoma in adults and adolescents aged 12 years and older
- Advanced renal cell carcinoma (kidney cancer) in adults — as first-line treatment for intermediate/poor-risk patients
- Malignant pleural mesothelioma (cancer affecting the lining of the lungs) in adults — as first-line treatment
- Advanced colorectal cancer (colon or rectal cancer) with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) in adults
- Advanced esophageal cancer (esophageal squamous cell carcinoma) in adults
- Unresectable or advanced hepatocellular carcinoma (liver cancer) in adults
In combination with nivolumab and chemotherapy:
- Advanced non-small cell lung cancer (NSCLC) in adults — as first-line treatment
When YERVOY is given in combination with other cancer medicines, it is essential that you also read the patient information leaflet for those medicines. Discuss any questions you have about your treatment regimen with your oncologist.
What Should You Know Before Taking YERVOY?
Before starting YERVOY, your oncologist will conduct a thorough assessment of your overall health. You should not receive YERVOY if you are allergic to ipilimumab or any of its inactive ingredients. Several pre-existing conditions require careful evaluation before treatment begins.
Contraindications
YERVOY must not be administered if you have a known hypersensitivity (allergy) to ipilimumab or to any of the excipients in the formulation (tris hydrochloride, sodium chloride, mannitol, pentetic acid, polysorbate 80, sodium hydroxide, hydrochloric acid, and water for injections). If you are uncertain whether you have an allergy to any of these components, discuss this with your oncologist before treatment.
Warnings and Precautions
YERVOY works by activating your immune system, which means it can cause inflammation in virtually any organ. These immune-mediated adverse reactions can be severe or even life-threatening. Speak to your doctor immediately if you experience any of the following:
- Heart problems: Changes in heart rhythm or rate, irregular heartbeat, chest pain
- Intestinal inflammation (colitis): Diarrhea, blood in stools, abdominal pain or tenderness
- Lung inflammation (pneumonitis): Breathing difficulties, persistent cough, chest tightness
- Liver inflammation (hepatitis): Yellowing of eyes or skin (jaundice), right-sided abdominal pain, unusual fatigue
- Severe skin reactions: Widespread rash, peeling skin, blisters, fever with skin changes
- Nerve inflammation (neuropathy): Muscle weakness, numbness, tingling in hands or feet
- Kidney inflammation (nephritis): Decreased urine output, blood in urine, swelling
- Endocrine disorders: Severe headache, visual disturbances, extreme fatigue, unexplained weight changes
- Heart muscle inflammation (myocarditis): Chest pain, shortness of breath, irregular heartbeat
- Eye inflammation: Eye redness, pain, vision changes, blurred vision
These symptoms can appear weeks or even months after your last dose. Do not attempt to treat these symptoms with over-the-counter medications. Your oncologist may prescribe corticosteroids or other immunosuppressive agents to manage these reactions, and may delay or permanently discontinue YERVOY treatment depending on the severity.
Before treatment, inform your oncologist if you have:
- An autoimmune disease (a condition where the body attacks its own cells, such as lupus, rheumatoid arthritis, or inflammatory bowel disease)
- A chronic viral liver infection, including hepatitis B (HBV) or hepatitis C (HCV)
- HIV/AIDS
- A history of severe skin reactions from previous cancer treatments
- A history of lung inflammation
- A history of organ transplantation (ipilimumab may trigger organ rejection)
Children and Adolescents
YERVOY should not be used in children under 12 years of age. For adolescents aged 12 years and older, YERVOY is only approved for the treatment of melanoma (alone or in combination with nivolumab). All other cancer indications are approved for adults only.
Pregnancy and Breastfeeding
Inform your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. YERVOY should not be used during pregnancy unless your oncologist determines that the potential benefit justifies the potential risk to the fetus. The effects of ipilimumab on pregnant women are not fully characterized, but based on its mechanism of action, it may potentially harm an unborn baby by disrupting fetal immune tolerance.
Women of childbearing potential must use effective contraception during YERVOY treatment and for at least 3 months after the last dose. If you become pregnant during treatment, contact your oncologist immediately.
It is not known whether ipilimumab is excreted in breast milk in clinically relevant amounts. Significant exposure of the infant through breast milk is not expected. Discuss with your doctor whether you can breastfeed during or after YERVOY treatment.
Driving and Operating Machinery
Do not drive or operate machinery after receiving YERVOY unless you are certain you feel well. Fatigue and weakness are very common side effects that can impair your ability to drive safely or operate heavy equipment.
YERVOY contains sodium. The 10 ml vial contains 23 mg sodium (1.15% of the WHO recommended maximum daily intake for adults). The 40 ml vial contains 92 mg sodium (4.60% of the maximum daily intake). Inform your doctor if you are on a low-sodium diet.
How Does YERVOY Interact with Other Drugs?
YERVOY can interact with several medications, including corticosteroids, anticoagulants, and vemurafenib. It is essential to inform your oncologist about all medications you are taking before starting treatment. Do not take new medications during treatment without consulting your doctor first.
Drug interactions with YERVOY are clinically significant because they can either reduce the effectiveness of immunotherapy or increase the risk of serious adverse reactions. The most important interactions are outlined below.
| Interacting Drug | Type | Clinical Effect | Recommendation |
|---|---|---|---|
| Vemurafenib (Zelboraf) | Major | Increased hepatotoxicity and skin adverse reactions when given sequentially | Combination is not recommended; avoid concurrent or sequential use |
| Corticosteroids (systemic) | Moderate | May reduce YERVOY efficacy if used before treatment initiation | Avoid before starting YERVOY; may be used after to manage immune-related adverse events |
| Anticoagulants (blood thinners) | Moderate | Increased risk of gastrointestinal hemorrhage | Use with caution; monitor for signs of bleeding |
| Other immunosuppressants | Moderate | May reduce the immune-activating effect of YERVOY | Avoid concurrent use unless managing adverse reactions |
| Live vaccines | Major | Risk of infection due to altered immune function | Avoid live vaccines during and shortly after treatment |
Always inform your oncologist and pharmacist about all medications, supplements, and herbal products you are currently taking. Do not start any new medication during your YERVOY treatment without first consulting your doctor.
What Is the Correct Dosage of YERVOY?
YERVOY is administered as a 30-minute intravenous infusion in a hospital or clinic under the supervision of an experienced oncologist. The dose is calculated based on your body weight in kilograms. The specific dose and schedule depend on the type of cancer being treated and whether YERVOY is used alone or in combination with other drugs.
YERVOY is never self-administered. It is always given by trained healthcare professionals in a clinical setting. Before each infusion, your blood will be tested to check for any signs of immune-related reactions.
Monotherapy (YERVOY Alone) — Melanoma
Advanced Melanoma — Adults and Adolescents (≥12 years)
Dose: 3 mg/kg body weight
Schedule: Once every 3 weeks for a total of 4 doses
Administration: 30-minute intravenous infusion
The total amount of YERVOY you receive is calculated from your body weight. More than one vial may be needed to achieve the correct dose. Each dose is diluted with sodium chloride 0.9% or glucose 5% before infusion.
Combination Therapy with Nivolumab
When used in combination, YERVOY is given during an initial combination phase, followed by nivolumab alone in a monotherapy phase. The order of administration is: nivolumab first, then YERVOY.
| Cancer Type | YERVOY Dose | Schedule | Combination Phase |
|---|---|---|---|
| Advanced Melanoma | 3 mg/kg | Every 3 weeks | 4 doses, then nivolumab monotherapy |
| Renal Cell Carcinoma | 1 mg/kg | Every 3 weeks | 4 doses, then nivolumab monotherapy |
| Colorectal Cancer (MSI-H/dMMR) | 1 mg/kg | Every 3 weeks | 4 doses, then nivolumab monotherapy |
| Pleural Mesothelioma | 1 mg/kg | Every 6 weeks | Ongoing (no switch to monotherapy) |
| Esophageal Cancer | 1 mg/kg | Every 6 weeks | Ongoing (no switch to monotherapy) |
| Hepatocellular Carcinoma | 3 mg/kg | Every 3 weeks | Up to 4 doses, then nivolumab monotherapy |
| NSCLC (+ chemotherapy) | 1 mg/kg | Every 6 weeks | With chemo for 2 cycles, then ipi + nivo |
Missed Dose
It is very important to attend all scheduled appointments for your YERVOY infusions. If you miss an appointment, contact your oncologist as soon as possible to reschedule. Missing doses may affect the effectiveness of your treatment.
Stopping Treatment
Do not stop YERVOY treatment without discussing it with your oncologist. Discontinuing treatment prematurely may reduce the drug's effectiveness. However, your doctor may decide to delay or permanently stop treatment if you develop serious immune-mediated adverse reactions.
What Are the Side Effects of YERVOY?
Like all medicines, YERVOY can cause side effects. Because it works by activating the immune system, many side effects are immune-mediated and involve inflammation of various organs. These can range from mild to life-threatening. Report any new or worsening symptoms to your oncologist immediately.
The following side effects have been reported in patients receiving ipilimumab 3 mg/kg as monotherapy. When YERVOY is used in combination with nivolumab and/or chemotherapy, additional or more frequent side effects may occur.
Do not attempt to treat any side effects with over-the-counter medications without first consulting your oncologist. Many immune-mediated reactions require specific medical management, and self-treatment can mask symptoms or delay appropriate care.
YERVOY Monotherapy Side Effects
Very Common
May affect more than 1 in 10 patients
- Decreased appetite
- Diarrhea (watery, loose, or soft stools), vomiting, nausea, constipation, abdominal pain
- Skin rash, itching (pruritus)
- Pain in muscles, bones, ligaments, tendons, and nerves (musculoskeletal pain)
- Fatigue or weakness, injection site reactions, fever, edema (swelling), pain
Common
May affect up to 1 in 10 patients
- Serious bacterial infection of the blood (sepsis), urinary tract infection, respiratory tract infection
- Decreased red blood cells, white blood cells, or platelets
- Decreased thyroid function, pituitary dysfunction or inflammation
- Dehydration, confusion, depression
- Fluid accumulation in the brain, nerve damage, dizziness, headache, blurred vision, eye pain
- Irregular or abnormal heartbeat, low blood pressure
- Shortness of breath (dyspnea), cough
- Gastrointestinal bleeding, colitis (intestinal inflammation), heartburn, mouth ulcers
- Abnormal liver function, skin inflammation, vitiligo (loss of skin color), hair loss, dry skin, night sweats
- Joint pain (arthralgia), muscle cramps, joint inflammation (arthritis)
- Kidney failure, chills, weight loss, flu-like symptoms
Uncommon
May affect up to 1 in 100 patients
- Septic shock, meningeal inflammation, intestinal perforation, pancreatitis, pneumonia
- Allergic reactions, increased eosinophils
- Adrenal insufficiency, overactive thyroid, sex hormone gland defects
- Tumor lysis syndrome
- Guillain-Barré syndrome, nerve inflammation in the brain, difficulty coordinating movement, tremor
- Eye inflammation (conjunctivitis, uveitis), bleeding in the eye
- Blood vessel inflammation, restricted blood supply to extremities
- Severe breathing difficulties, fluid in the lungs
- Liver failure, enlarged liver, jaundice
- Toxic epidermal necrolysis (severe, potentially fatal skin peeling), Stevens-Johnson syndrome, DRESS syndrome
- Muscle inflammation (myositis), kidney inflammation, bladder inflammation
- Multi-organ failure
Rare and Very Rare
May affect fewer than 1 in 1,000 patients
- Inflammatory blood vessel disease (temporal arteritis)
- Thyroid gland swelling (thyroiditis)
- Psoriasis, erythema multiforme
- Vogt-Koyanagi-Harada syndrome, serous retinal detachment
- Type 1 diabetes or diabetic ketoacidosis
- Myasthenia gravis (severe muscle weakness)
- Exocrine pancreatic insufficiency, celiac disease
- Life-threatening anaphylaxis (very rare)
- Hemophagocytic lymphohistiocytosis (HLH)
- Transplant organ rejection
- Myelitis (spinal cord inflammation)
Combination Therapy Side Effects
When YERVOY is used together with nivolumab and/or chemotherapy, additional side effects may occur, and existing side effects may be more frequent or severe. Key additional effects include:
- Very common (additional): Upper respiratory tract infection, decreased thyroid function, high or low blood sugar, headache, skin rash with blisters, joint pain
- Common (additional): Pneumonia, bronchitis, thyroid swelling, diabetes, peripheral neuropathy, dry eyes, increased heart rate, high blood pressure, pneumonitis, pancreatitis, dry mouth, gastritis, psoriasis, muscle weakness, kidney failure
- Uncommon (additional): Diabetic ketoacidosis, myocarditis (heart muscle inflammation), autoimmune neuropathy, myasthenia gravis, duodenal inflammation, sarcoidosis
- Rare (additional): Aseptic meningitis, Guillain-Barré syndrome, myelitis, Sjögren's syndrome, rhabdomyolysis, lichen sclerosus, Vogt-Koyanagi-Harada syndrome, bladder inflammation, celiac disease
Changes in Blood Tests
YERVOY may cause changes in laboratory test results, including:
- Changes in blood cell counts (red cells, white cells, and platelets)
- Abnormal hormone and liver enzyme levels
- Abnormal kidney function values (increased creatinine)
- Abnormal levels of calcium, sodium, phosphate, or potassium
- Presence of blood or protein in urine
- Presence of antibodies directed against the body's own cells
If you experience any side effects, including those not listed here, report them to your healthcare provider. You can also report side effects to your national medicines regulatory authority. Reporting helps monitor the ongoing benefit-risk balance of the medicine.
How Should You Store YERVOY?
YERVOY must be stored in a refrigerator at 2–8°C (36–46°F). It must not be frozen. Keep in the original packaging to protect from light. As YERVOY is administered in a healthcare setting, storage is typically handled by hospital pharmacy staff.
Keep YERVOY out of the sight and reach of children. Do not use YERVOY after the expiry date stated on the carton and label after “EXP.” The expiry date refers to the last day of the stated month.
Storage conditions:
- Store in a refrigerator (2°C–8°C / 36°F–46°F)
- Do not freeze
- Store in the original packaging to protect from light
After opening or dilution: From a microbiological point of view, the product should be used immediately. Chemical and physical stability has been demonstrated for up to 24 hours at room temperature (20–25°C) or refrigerated (2–8°C). Do not save unused portions of the infusion solution for later use. Dispose of any unused product according to local regulations.
What Does YERVOY Contain?
YERVOY contains ipilimumab as the active substance at a concentration of 5 mg/ml. It is a clear to slightly opalescent, colorless to pale yellow liquid that may contain a few light particles.
Active substance: Ipilimumab — each ml of concentrate contains 5 mg ipilimumab. A 10 ml vial contains 50 mg ipilimumab. A 40 ml vial contains 200 mg ipilimumab.
Inactive ingredients (excipients):
- Tris hydrochloride (buffer)
- Sodium chloride (tonicity agent)
- Mannitol (E421) (stabilizer)
- Pentetic acid (chelating agent)
- Polysorbate 80 (surfactant)
- Sodium hydroxide (pH adjuster)
- Hydrochloric acid (pH adjuster)
- Water for injections
Available pack sizes: YERVOY is available in packs containing either 1 vial of 10 ml or 1 vial of 40 ml. Not all pack sizes may be marketed in all countries.
Marketing authorization holder: Bristol-Myers Squibb Pharma EEIG, Plaza 254, Blanchardstown Corporate Park 2, Dublin 15, D15 T867, Ireland.
Frequently Asked Questions About YERVOY
YERVOY is used to treat several types of advanced cancer. As monotherapy, it treats advanced melanoma in adults and adolescents 12 years and older. In combination with nivolumab, it is approved for advanced melanoma, renal cell carcinoma, malignant pleural mesothelioma, MSI-H/dMMR colorectal cancer, esophageal squamous cell carcinoma, and hepatocellular carcinoma. Combined with nivolumab and chemotherapy, it treats advanced non-small cell lung cancer.
The most serious side effects are immune-mediated reactions, which occur because YERVOY activates the immune system. These include severe colitis (intestinal inflammation that can lead to perforation), hepatitis (liver inflammation potentially leading to liver failure), severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), neuropathy (including Guillain-Barré syndrome), endocrine disorders (hypophysitis, adrenal insufficiency, thyroid disorders, type 1 diabetes), myocarditis (heart muscle inflammation), and nephritis (kidney inflammation). These reactions can be life-threatening and require immediate medical attention.
YERVOY is given as an intravenous infusion over 30 minutes in a hospital or clinic. When used alone for melanoma, you receive 4 doses given every 3 weeks. When used in combination with nivolumab, the treatment typically starts with a combination phase (usually 4 doses of both drugs every 3 weeks), followed by nivolumab alone. For some cancer types like mesothelioma and esophageal cancer, ipilimumab is given every 6 weeks on an ongoing basis alongside nivolumab.
YERVOY should not be used during pregnancy unless your oncologist specifically determines the benefits outweigh the risks. Based on its mechanism of action, ipilimumab may potentially harm an unborn baby. Women of childbearing potential must use effective contraception during treatment and for at least 3 months after the last dose. While significant infant exposure through breast milk is not expected, discuss breastfeeding decisions with your oncologist.
Both YERVOY and OPDIVO are immune checkpoint inhibitors, but they target different checkpoints. YERVOY (ipilimumab) blocks CTLA-4, which primarily regulates T-cell activation in the early stages of the immune response. OPDIVO (nivolumab) blocks PD-1, which regulates T-cell activity in the tumor microenvironment. Together, they provide complementary immune activation, which is why the combination is more effective than either drug alone for many cancer types.
YERVOY must be stored in a refrigerator at 2–8°C and must not be frozen. It should be kept in its original packaging to protect from light. Since YERVOY is administered in a healthcare setting, storage is typically handled by hospital pharmacy staff. Once opened or diluted, it should be used within 24 hours whether stored at room temperature or refrigerated.
References
- European Medicines Agency (EMA). YERVOY (ipilimumab) — Summary of Product Characteristics. Last updated 2025. Available at: ema.europa.eu/en/medicines/human/EPAR/yervoy
- U.S. Food and Drug Administration (FDA). YERVOY (ipilimumab) Prescribing Information. Bristol-Myers Squibb, 2024.
- Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711-723. doi:10.1056/NEJMoa1003466
- Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2019;381(16):1535-1546. doi:10.1056/NEJMoa1910836
- Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277-1290. doi:10.1056/NEJMoa1712126
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Melanoma: Cutaneous. Version 2.2025.
- Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378(2):158-168. doi:10.1056/NEJMra1703481
- World Health Organization (WHO). WHO Model List of Essential Medicines — 23rd Edition, 2023.
- Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2021;39(36):4073-4126. doi:10.1200/JCO.21.01440
Editorial Team
This article has been written and medically reviewed by the iMedic Medical Editorial Team, consisting of licensed physicians and pharmacists with expertise in oncology, immunotherapy, and clinical pharmacology.
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