Autoimmune Endocrine Dysfunctions Associated with Cancer Immunotherapies.

Abstract

Immune checkpoint inhibitors block the checkpoint molecules. Different types of cancer immune checkpoint inhibitors have been approved recently: CTLA-4 monoclonal antibodies (as ipilimumab); anti-PD-1 monoclonal antibodies (as pembrolizumab and nivolumab); and anti-PD-L1 monoclonal antibodies (as atezolizumab, avelumab, and durmalumab). We collect recent published results about autoimmune endocrine dysfunctions associated with cancer antibody immunotherapies. These agents cause a raised immune response leading to immune-related adverse events (irAEs), varying from mild to fatal, based on the organ system and severity. Immune-related endocrine toxicities are usually irreversible in 50% of cases, and include hypophysitis, thyroid dysfunctions, type 1 diabetes mellitus, and adrenal insufficiency. Anti-PD-1-antibodies are more frequently associated with thyroid dysfunctions (including painless thyroiditis, hypothyroidism, thyrotoxicosis, or thyroid storm), while the most frequent irAE related to anti-CTLA-4-antibodies is hypophysitis. The combination of anti-CTLA-4 and anti-PD-1 antibodies is associated with a 30% chance of irAEs. Symptoms and clinical signs vary depending on the target organ. IrAEs are usually managed by an oncological therapist, but in more challenging circumstances (i.e., for new onset insulin-dependent diabetes, hypoadrenalism, gonadal hormones dysfunctions, or durable hypophysitis) an endocrinologist is needed.

• Authors: Silvia Martina Ferrari, Poupak Fallahi, Giusy Elia, Francesca Ragusa, Ilaria Ruffilli, Armando Patrizio, Maria Rosaria Galdiero, Enke Baldini, Salvatore Ulisse, Gianni Marone, Alessandro Antonelli
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 10 (May 24 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 31137683 (Publication Type: Journal Article, Review)

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents

Topics

• Animals
• Antibodies, Monoclonal (adverse effects)
• Antineoplastic Agents (adverse effects)
• Autoimmune Diseases (etiology)
• Endocrine System Diseases (etiology)
• Humans
• Immunotherapy (adverse effects)
• Neoplasms (therapy)