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Immune checkpoint inhibitor therapy associated hypophysitis.

Mahzari M, Liu D, Arnaout A, Lochnan H - Clin Med Insights Endocrinol Diabetes (2015)

Bottom Line: The clinical features of six patients with ipilimumab-induced hypophysitis (IH) are described.Endocrinologists should anticipate a significant increase in the incidence of autoimmune hypophysitis.Strategies for early detection of IH and long-term management should be considered.

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Ottawa and the Ottawa Hospital, Ottawa, Canada.

ABSTRACT
Ipilimumab is a monoclonal antibody directed against CTLA4 T-lymphocyte antigen used as cancer therapy. Immune-related adverse events are common side effects and may include hypophysitis-related hypopituitarism. The clinical features of six patients with ipilimumab-induced hypophysitis (IH) are described. The clinical features of IH reported in clinical trials, including the incidence of IH by gender and the likelihood of adrenal axis recovery, are summarized. Following the development of IH, most patients remain on glucocorticoid replacement despite efforts to withdraw therapy. Analysis of gender information in published clinical trials suggests that men are more prone to developing IH than women, and few patients fully recover the pituitary-adrenal axis function. Ipilimumab and other drugs within its class are likely to be used to treat many forms of cancer. Endocrinologists should anticipate a significant increase in the incidence of autoimmune hypophysitis. Strategies for early detection of IH and long-term management should be considered.

No MeSH data available.


Related in: MedlinePlus

Ipilimumab’s mechanism of action. CD28 (T-lymphocyte costimulatory receptor) and CTLA4 (T lymphocyte coinhibitory receptor) have a common tumor antigen ligand (B7). CTLA4, when expressed on T-cell membrane, has a higher affinity for B7 binding, which leads to cancer immune tolerance. Ipilimumab blocks CTLA4 and leads to anticancer immune effects through T-lymphocyte activation.
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f1-cmed-8-2015-021: Ipilimumab’s mechanism of action. CD28 (T-lymphocyte costimulatory receptor) and CTLA4 (T lymphocyte coinhibitory receptor) have a common tumor antigen ligand (B7). CTLA4, when expressed on T-cell membrane, has a higher affinity for B7 binding, which leads to cancer immune tolerance. Ipilimumab blocks CTLA4 and leads to anticancer immune effects through T-lymphocyte activation.

Mentions: Monoclonal antibodies against cytotoxic lymphocyte antigen 4 (CTLA4), ipilimumab in particular, inhibit the CTLA4-mediated inhibition of T lymphocytes, leading to an immune-mediated antitumor response (Fig. 1). Ipilimumab is now an approved therapy for metastatic melanoma because significant objective responses and overall survival benefit have been demonstrated with its use.1 Immune-related adverse events (IRAEs) are recognized complications of this treatment. The most commonly reported IRAEs are enterocolitis, skin rash (including vitiligo), and hepatitis. The most common endocrinopathy associated with ipilimumab use appears to be hypophysitis with hypopituitarism, which has been reported in 0%–17%, followed by hypo- and hyperthyroidism secondary to thyroiditis in 2.7% and 0.3%, respectively, and primary adrenal insufficiency in 2.1%.1


Immune checkpoint inhibitor therapy associated hypophysitis.

Mahzari M, Liu D, Arnaout A, Lochnan H - Clin Med Insights Endocrinol Diabetes (2015)

Ipilimumab’s mechanism of action. CD28 (T-lymphocyte costimulatory receptor) and CTLA4 (T lymphocyte coinhibitory receptor) have a common tumor antigen ligand (B7). CTLA4, when expressed on T-cell membrane, has a higher affinity for B7 binding, which leads to cancer immune tolerance. Ipilimumab blocks CTLA4 and leads to anticancer immune effects through T-lymphocyte activation.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4376202&req=5

f1-cmed-8-2015-021: Ipilimumab’s mechanism of action. CD28 (T-lymphocyte costimulatory receptor) and CTLA4 (T lymphocyte coinhibitory receptor) have a common tumor antigen ligand (B7). CTLA4, when expressed on T-cell membrane, has a higher affinity for B7 binding, which leads to cancer immune tolerance. Ipilimumab blocks CTLA4 and leads to anticancer immune effects through T-lymphocyte activation.
Mentions: Monoclonal antibodies against cytotoxic lymphocyte antigen 4 (CTLA4), ipilimumab in particular, inhibit the CTLA4-mediated inhibition of T lymphocytes, leading to an immune-mediated antitumor response (Fig. 1). Ipilimumab is now an approved therapy for metastatic melanoma because significant objective responses and overall survival benefit have been demonstrated with its use.1 Immune-related adverse events (IRAEs) are recognized complications of this treatment. The most commonly reported IRAEs are enterocolitis, skin rash (including vitiligo), and hepatitis. The most common endocrinopathy associated with ipilimumab use appears to be hypophysitis with hypopituitarism, which has been reported in 0%–17%, followed by hypo- and hyperthyroidism secondary to thyroiditis in 2.7% and 0.3%, respectively, and primary adrenal insufficiency in 2.1%.1

Bottom Line: The clinical features of six patients with ipilimumab-induced hypophysitis (IH) are described.Endocrinologists should anticipate a significant increase in the incidence of autoimmune hypophysitis.Strategies for early detection of IH and long-term management should be considered.

View Article: PubMed Central - PubMed

Affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Ottawa and the Ottawa Hospital, Ottawa, Canada.

ABSTRACT
Ipilimumab is a monoclonal antibody directed against CTLA4 T-lymphocyte antigen used as cancer therapy. Immune-related adverse events are common side effects and may include hypophysitis-related hypopituitarism. The clinical features of six patients with ipilimumab-induced hypophysitis (IH) are described. The clinical features of IH reported in clinical trials, including the incidence of IH by gender and the likelihood of adrenal axis recovery, are summarized. Following the development of IH, most patients remain on glucocorticoid replacement despite efforts to withdraw therapy. Analysis of gender information in published clinical trials suggests that men are more prone to developing IH than women, and few patients fully recover the pituitary-adrenal axis function. Ipilimumab and other drugs within its class are likely to be used to treat many forms of cancer. Endocrinologists should anticipate a significant increase in the incidence of autoimmune hypophysitis. Strategies for early detection of IH and long-term management should be considered.

No MeSH data available.


Related in: MedlinePlus