Ipilimumab, marketed with the brand name Yervoy, is a cancer treatment that falls under the category of immunotherapy. It is designed to help a person’s immune system better recognize and attack cancer cells. This approach differs from traditional chemotherapy, which directly targets and kills rapidly dividing cells. Ipilimumab is a type of immunotherapy known as an immune checkpoint inhibitor, a treatment method that has become more common since its FDA approval in 2011.
How Ipilimumab Works
The human immune system has natural regulators known as immune checkpoints. These checkpoints function like brakes, preventing the immune system from becoming overly aggressive and damaging healthy tissues. One of these checkpoint proteins, found on the surface of immune cells called T-cells, is Cytotoxic T-Lymphocyte-Associated protein 4, or CTLA-4. CTLA-4 helps to maintain immune balance by deactivating T-cells when they are no longer needed.
Some cancer cells have developed ways to take advantage of this natural braking system to protect themselves. They can effectively press down on the CTLA-4 brake, which stops T-cells from recognizing and destroying the tumor. This allows the cancer to grow unchecked, hidden from the body’s natural defenses.
Ipilimumab is a monoclonal antibody, a manufactured protein designed to target and block the CTLA-4 protein. By binding to CTLA-4, it prevents the protein from engaging with its partners on other cells, which effectively releases the brake on the T-cell. This action does not kill cancer cells directly but empowers the immune system. With the inhibitory signal removed, T-cells are activated and can multiply, allowing them to mount a more forceful and sustained attack against tumor cells.
Cancers Treated with Ipilimumab
Ipilimumab is approved for the treatment of several types of cancer, particularly those in advanced or metastatic stages. Its first approval was for metastatic melanoma, a form of skin cancer that has spread to other parts of the body. It is also used to treat certain cases of advanced renal cell carcinoma, the most common type of kidney cancer in adults.
The medication is also an option for specific subtypes of other cancers, often depending on genetic markers within the tumor or a patient’s prior treatment history. These include:
- Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer that has progressed following other treatments.
- Non-small cell lung cancer (NSCLC).
- Malignant pleural mesothelioma.
- Esophageal cancer.
Ipilimumab is frequently administered in combination with another immunotherapy drug, nivolumab. Nivolumab blocks a different immune checkpoint protein, PD-1. Combining these drugs has been shown to produce a more robust anti-tumor response in certain cancers than either drug used alone. This dual-checkpoint blockade attacks the cancer from two different angles, which can lead to improved outcomes.
Administration and Treatment Process
Ipilimumab is given to patients as an intravenous (IV) infusion. The procedure takes place in a clinical environment, like a hospital or infusion center, under medical supervision. The liquid drug is dripped through a tube into a vein, entering the bloodstream directly.
A standard infusion lasts between 30 and 90 minutes. During this time, patients are monitored by nursing staff for any immediate reactions to the medication.
The treatment schedule depends on the cancer type and if it is part of a combination therapy. A common regimen for melanoma, when used alone, involves one infusion every three weeks for a total of four doses. When combined with nivolumab, the schedule might involve ipilimumab given at a lower dose every three or six weeks alongside more frequent nivolumab infusions. The treatment plan is determined by the patient’s oncology team.
Potential Side Effects
By boosting the immune system, ipilimumab can cause activated T-cells to attack healthy tissues, leading to side effects. These reactions are known as immune-related adverse events and can affect nearly any part of the body. Side effects can appear during treatment or even weeks to months after the final dose.
Common skin-related side effects include rash, itching, or vitiligo, which is the loss of skin color in patches. While many skin reactions are mild, severe reactions can occur in rare instances. Any new or worsening skin changes should be reported to a doctor.
The gastrointestinal tract is also affected. Diarrhea is a common symptom, but it can signal a more serious inflammation of the colon called colitis. Symptoms of colitis include abdominal pain, cramping, and blood or mucus in the stool. Untreated, severe colitis can lead to an intestinal perforation, which is a medical emergency.
Inflammation can occur in various glands and organs. Liver inflammation, or hepatitis, may be detected by blood tests showing elevated liver enzymes. The endocrine glands are also susceptible. Inflammation of the pituitary gland, or hypophysitis, can cause headaches and hormone deficiencies. The thyroid gland can also be affected, leading to hyperthyroidism or hypothyroidism.
Due to the wide range of potential side effects, patients should report any new symptoms to their healthcare team immediately. Early detection and management are important for controlling these adverse events. This often involves using corticosteroid medications to suppress the immune system and prevent reactions from becoming severe.