Nivolumab

Approved Uses

Nivolumab is used to treat several different types of cancer. It is frequently prescribed when cancer is advanced, has spread to other parts of the body (metastatic), or cannot be removed by surgery. It may also be used as an adjuvant treatment, which is given after surgery to help lower the risk of the cancer coming back.

Commonly treated conditions include:

• Melanoma: A type of skin cancer.
• Lung Cancer: Specifically non-small cell lung cancer.
• Kidney Cancer: Renal cell carcinoma.
• Bladder Cancer: Urothelial carcinoma of the bladder or urinary tract.
• Blood Cancer: Classical Hodgkin lymphoma.
• Head and Neck Cancer: Squamous cell carcinoma.
• Digestive System Cancers: Including esophageal, stomach (gastric), and liver (hepatocellular) cancers.
• Colorectal Cancer: Specifically for tumors with certain genetic features known as MSI-H or dMMR.
• Mesothelioma: Malignant pleural mesothelioma.

How It Is Used

Nivolumab may be administered alone or in combination with other treatments. It is often paired with another immunotherapy drug called ipilimumab or used alongside chemotherapy. While typically given as an intravenous infusion, certain formulations may be administered as an injection under the skin.

Immune System Activation

Nivolumab belongs to a class of drugs known as monoclonal antibodies and immune checkpoint inhibitors. Its primary role is to boost the body's natural immune response against cancer cells.

Targeting the PD-1 Pathway

The immune system uses specific "checkpoints" to prevent it from attacking healthy cells. One of these checkpoints involves a protein called programmed death-1 (PD-1) found on the surface of T-cells, which are a type of white blood cell. When certain proteins on cancer cells bind to PD-1, they send a signal to the T-cell to stop its attack, effectively allowing the cancer to hide from the immune system.

Nivolumab works by:

• Blocking the PD-1 receptor: The medication attaches to the PD-1 protein on the T-cells.
• Preventing the "off" signal: By blocking this receptor, nivolumab prevents cancer cells from binding to the T-cells and switching them off.
• Restoring immune function: This allows the T-cells to remain active so they can find, target, and destroy cancer cells throughout the body.

In some treatment plans, nivolumab is used in combination with other immunotherapy drugs to further enhance the immune system's ability to recognize and fight specific types of tumors.

Common Side Effects

Many people receiving nivolumab experience mild to moderate side effects. These may include:

• Feeling tired or weak
• Muscle, bone, or joint pain
• Itching or skin rash
• Nausea, diarrhea, or constipation
• Decreased appetite and weight loss
• Cough or shortness of breath
• Upper respiratory tract infections
• Headache
• Fever or dizziness

Serious Side Effects

Nivolumab works by stimulating the immune system, which can sometimes cause it to attack healthy tissues and organs. These reactions can be severe or life-threatening and may occur during or after treatment. Seek medical attention immediately if you experience:

• Lung problems: New or worsening cough, chest pain, or shortness of breath.
• Intestinal problems: Severe stomach pain, diarrhea, or stools that are black, tarry, or contain blood or mucus.
• Liver problems: Yellowing of the skin or eyes, dark urine, severe nausea, or pain on the right side of the stomach.
• Hormone gland problems: Headaches that will not go away, extreme tiredness, weight changes, increased thirst or urination, or changes in mood or behavior.
• Kidney problems: Decrease in the amount of urine or blood in the urine.
• Skin reactions: Severe rash, itching, blistering, or peeling.
• Infusion reactions: Chills, shaking, dizziness, or fever during the injection.

Other serious complications can include inflammation of the brain (encephalitis), heart, or eyes. Contact your healthcare provider right away if you notice any new or unusual symptoms.

Immune-Mediated Side Effects

Nivolumab works by stimulating the immune system to attack cancer cells. However, it may also cause the immune system to attack healthy organs and tissues. These reactions can occur at any time during treatment or even after treatment has stopped. If these reactions become severe, treatment may be delayed or permanently discontinued.

• Lung problems: Inflammation of the lungs (pneumonitis) can cause new or worsening cough, chest pain, or shortness of breath.
• Intestinal problems: Inflammation of the colon (colitis) can lead to diarrhea, blood in the stool, or severe stomach pain.
• Liver problems: Hepatitis can cause yellowing of the skin or eyes (jaundice), dark urine, nausea, or pain on the right side of the stomach.
• Hormone gland problems: The drug can affect the thyroid, pituitary, and adrenal glands, as well as the pancreas (Type 1 diabetes). Symptoms may include extreme tiredness, weight changes, or increased thirst.
• Kidney problems: Nephritis can cause changes in the amount or color of urine, swelling in the ankles, or loss of appetite.
• Skin problems: Severe rashes, itching, or blistering may occur.

Infusion and Injection Reactions

Some patients may experience reactions while receiving the medication via intravenous infusion or subcutaneous injection. Symptoms can include chills, shaking, itching, rash, flushing, dizziness, fever, or difficulty breathing. Healthcare providers typically monitor patients during and after the administration to manage these reactions immediately.

Pregnancy and Breastfeeding

Nivolumab can cause harm to an unborn baby. Effective birth control is generally recommended during treatment and for at least 5 months after the final dose. It is not known if the medication passes into breast milk, so breastfeeding is typically discouraged during treatment and for several months following the last dose.

Stem Cell Transplant Complications

Patients who receive a stem cell transplant using donor cells (allogeneic) after treatment with nivolumab may have an increased risk of serious complications, including graft-versus-host disease. Healthcare providers will monitor for signs of these complications if a transplant is planned.

Pregnancy

Nivolumab can cause harm to an unborn baby. It is important to inform a healthcare provider if you are pregnant or planning to become pregnant before starting this medication. Individuals who can become pregnant should use effective birth control during treatment and for at least 5 months after the final dose of nivolumab.

Breastfeeding

It is not known whether nivolumab passes into human breast milk. Because of the potential for serious side effects in a nursing infant, breastfeeding is not recommended during treatment. Patients are generally advised to avoid breastfeeding while receiving nivolumab and for at least 5 months after the last dose.

Available Forms

Nivolumab is supplied in the following formulations for administration by medical staff:

• Intravenous Infusion: This form is a concentrated liquid solution that must be diluted before being infused into a vein.
• Subcutaneous Injection: This formulation combines nivolumab with hyaluronidase and is designed for injection under the skin.

Both formulations are provided in vials and are administered in a clinical setting, such as a hospital or infusion center.

FDA Approval Status

Nivolumab was first approved by the U.S. Food and Drug Administration (FDA) in December 2014. It is a programmed death receptor-1 (PD-1) blocking antibody. Since its initial approval, the FDA has expanded its use to include numerous types of cancer, often as a first-line or second-line treatment depending on the specific diagnosis and previous therapies.

Approved Indications

The FDA has approved nivolumab for several adult and pediatric indications, including:

• Unresectable or metastatic melanoma.
• Metastatic non-small cell lung cancer.
• Malignant pleural mesothelioma.
• Advanced renal cell carcinoma.
• Classical Hodgkin lymphoma.
• Squamous cell carcinoma of the head and neck.
• Urothelial carcinoma (bladder cancer).
• Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer.
• Hepatocellular carcinoma (liver cancer).
• Esophageal and gastric cancers.

Recent Regulatory Actions

In February 2025, the FDA approved a subcutaneous formulation of nivolumab and hyaluronidase-nvhy. This formulation is approved for many of the same indications as the intravenous version, offering a shorter administration time. Additionally, the FDA has approved specific combination therapies, such as nivolumab used with ipilimumab, for patients with certain types of liver cancer and colorectal cancer that have progressed after prior treatments.

Safety and Monitoring

Nivolumab does not currently carry a Boxed Warning. However, the FDA-approved labeling includes significant warnings regarding immune-mediated adverse reactions. These reactions can occur in the lungs, colon, liver, endocrine system, kidneys, or skin. Because these reactions can be severe or life-threatening, the FDA requires healthcare providers to monitor patients closely during and after treatment. Some approvals were granted under the accelerated approval pathway based on tumor response rate and durability of response, and continued approval may be contingent upon verification of clinical benefit in confirmatory trials.

Factors Influencing Cost

The total cost of nivolumab treatment depends on several factors, including the specific medical condition being treated and the required dosage. Because the medication is administered by a healthcare professional in a clinical setting, costs typically include both the drug itself and fees for the medical facility and professional services.

• Administration Method: Nivolumab may be given as an intravenous infusion or a subcutaneous injection, which can affect the overall cost of administration.
• Combination Therapy: In many cases, nivolumab is used alongside other medications, such as ipilimumab, which will increase the total cost of the treatment cycle.

Insurance and Financial Support

Most insurance plans, including Medicare and Medicaid, provide coverage for nivolumab when used for FDA-approved indications. However, patients may be responsible for out-of-pocket costs such as deductibles or co-payments. Many pharmaceutical companies offer patient assistance programs or co-pay cards to help eligible individuals manage these expenses.