Immune checkpoint inhibitors-induced autoimmunity: The impact of gender

Objective To evaluate prevalence and clinical features of immune-related adverse events (irAEs) to immune checkpoint inhibitors (ICIs) in accordance with the gender of treated cancer patients. Methods A systematic review of the medical literature was conducted by searching all available clinical data up to December 2019 in several databases using a combination of MESH terms related to immune checkpoint inhibitors, autoimmunity, and gender. Analyzed data were related to all FDA approved ICIs and respective indications in cancer. Results According to data from the literature, male display a slightly lower frequencies of ICIs-related endocrinopathies compared with females, specifically thyroid dysfunction. On the contrary, ICIs-hypophysitis has been reported at higher rates among males compared with females. ICI-induced Sicca/Sjogren’s syndrome showed a more frequent occurrence in men than the idiopathic primary form. No differences in gender distribution seem to arise in hematologic and gastrointestinal-irAEs. Interestingly, the gender distribution of neurologic and vascular ICIs-irAEs appears male-dominant. Conclusions The present systematic review highlights for the first time that the distribution of patients experiencing irAEs associated with ICIs changes among the genders according to the specific drug used, the frequency of the cancer and of the autoimmune conditions in the general population.