Ipilimumab

ipilimumab

 (ih-pih-LIH-myoo-mab)A drug used with nivolumab to treat a certain type of colorectal cancer that has mutations (changes) in genes involved in DNA repair. It is also used with nivolumab in some patients to treat advanced renal cell carcinoma that has not already been treated. Ipilimumab is also used alone to treat melanoma that cannot be removed by surgery or has spread to other parts of the body. It is also used as adjuvant therapy to treat melanoma in the skin and lymph nodes in patients who have already had surgery. It is also being studied in the treatment of other types of cancer. Ipilimumab binds to a substance called CTLA-4, which is found on T cells (a type of white blood cell). Ipilimumab may block CTLA-4 and help the immune system kill cancer cells. It is a type of monoclonal antibody and a type of immune checkpoint inhibitor. Also called MDX-010 and Yervoy.

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Ipilimumab

Liver safety of Ipilimumab

Ipilimumab has major side effects, many of which can be serious and life threatening including acute liver injury.   

Mechanism of action of Ipilimumab

Ipilimumab (ip” i lim’ ue mab) is a human recombinant monoclonal immunoglobulin G1 antibody to the cytotoxic T lymphocyte antigen-4 (CTLA-4) which is used in cancer immunotherapy.  The CTLA-4 antigen is an important check-point molecule that modulates and down regulates T cell responses.  Inhibition of CTLA on the surface of activated T cells prevents its binding to the costimulatory factor B7, which allows for a continued activation and proliferation of T cells.  The subsequent enhancement of cytotoxic reactivity may play a beneficial role in cancer immunotherapy and can break immunological tolerance.  In several large multicenter studies, ipilimumab therapy resulted in a prolongation of survival in patients with advanced, metastatic or unresectable malignant melanoma, and a proportion of patients had a long term remission. 

FDA approval information for Ipilimumab

Ipilimumab was approved for use in advanced malignant melanoma in the United States in 2009, the first monoclonal check point inhibitor approved for use in treating neoplastic diseases.  Ipilimumab has also been evaluated in several other forms of cancer, including breast, colon, renal cell and pancreatic cancer, alone and in combination with other check point inhibitors such as nivolumab (anti-PD-1). 

Dosage and administration for Ipilimumab

Ipilimumab is available in liquid solution in 50 and 200 mg vials (5 mg/mL) under the brand name Yervoy.  The typical regimen is 3 mg/kg as an intravenous infusion every 3 weeks for a total of four doses. Ipililmumab is also approved for adjuvant therapy of melanoma where it is given in higher doses long-term. 

Side effects of Ipilimumab

Side effects are common and can be severe, life threatening and even fatal.  As many as 70% of treated patients develop immune related side effects as a result of immune enhancement including enterocolitis, dermatitis, endocrinopathy, neuropathy, nephritis and hepatitis.  Most of these reactions respond to immunosuppressive therapy.  Early recognition and prompt management of these side effects is an integral component of proper use of ipilimumab. 

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External links

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