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.
Highlights
Cancer immunotherapies unleash the immune system to control malignancy
immune checkpoint inhibitors (ICIs) show different adverse effects compared to chemotherapy and targeted therapies, and their combination with other ICIs or other treatments improves the effectiveness of immunotherapy [8,25]
The risk of immune-related adverse events (irAEs) correlated with the dosage, with all–grade irAEs showing an incidence of 61% for ipilimumab 3 mg/kg and 79% for ipilimumab (10 mg/kg)
Summary
Cancer immunotherapies unleash the immune system to control malignancy. The use of immunotherapy incorporated into adjuvant and neoadjuvant cancer therapies [1], a bispecific T–cell engager, immune checkpoint inhibitors (ICIs) [2,3], and Talimogene laherparepvec (T-VEC) (the first oncolytic immunotherapy) [4] have been recently approved. The evaluation of the possible use of antagonistic antibodies against CTLA–4 (as ipilimumab, the first approved immune checkpoint blockade drug) is ongoing, in order to inhibit the immune system tolerance to tumors, in this way possibly supplying a useful immunotherapy strategy for patients with cancer. Tremelimumab is another CTLA-4 inhibiting monoclonal antibody that it is not approved yet [12,13]. PD–1 promotes apoptosis (programmed cell death) of antigen–specific T–cells in lymph nodes and increases regulatory T-cell (antiflammatory, suppressive T cells) survival These agents cause a raised immune response leading to endocrine immune–related adverse events (irAEs) that vary from mild to fatal
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