Monoclonal antibodies that block the negative regulatory signals mediated by cytotoxic T- lymphocyte antigen-4 (CTLA-4).
Includes immunologic mechanisms of action may persist over prolonged periods of time, and provide durable disease control.
Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade with ipilimumab prolongs survival in patients with metastatic melanoma and the addition of GM-CSF results on longer overall survival and lower toxicity, but no difference in progression free survival.
CTLA-4 blocking antibodies undo T-cell inhibition at the activation step of the antitumor immune response.
Associated with autoimmune or autonflammatory side effects, designated as immune related adverse events, and include rash, colitis, or hepatitis, elevated liver function tests, uveitis, and hypophysitis.
Side effects are conceded nonspecific or cross reactive tissue damage caused by activated T cells.
Side effects of immune related adverse events are generally mild and self-limiting but severe events may occur, requiring supportive care and/or high-dose corticosteroid treatment to diminish CTLA-4 blockade effects.
The most irreversible toxicity is related to hypophysitis which may require endocrine replacement therapy.
Life-threatening diarrhea/colitis, and even bowel perforation may occur rarely.
Diarrhea is due to immune-mediated colitis and is the most common immune-related adverse reaction.
Diarrhea is dose limiting.
Severe diarrhea may require corticosteoids, mesalamine ot tumor necrosis factor for management.
Mortality rate from the use of anti-CTLA-4 treatment is approximately 1%.
The most common rash is a macular and papular exanthem affects the trunk and extremities.
Rash may be intensified by sun exposure.
Histologically the dermatitis has epidermal spongiosis, papillary edema and perivascular lymphocytic and eosinophilic infiltrates with predominantly CD 4+ T cells.
Hair depigmentation may occur starting with the eyebrows and then all body hair.
Median time to depigmentation 10 months.
Vitiligo may occur.
May experience alopecia areata.
Median time to depigmentation is 10 months.