Adverse Events as a Function of Biological Sex in a Multicenter Clinical Trial of Melanoma Vaccines

Background/Objective: Biological females experience more autoimmune disease than males and more treatment-related adverse events (TRAEs) after immune checkpoint blockade therapy. However, little is known about sex-related differences in TRAEs after cancer vaccines. Methods: The Mel44 clinical trial (NCT00118274) enrolled 167 eligible patients with high-risk melanoma to treatment with either of two melanoma multipeptide vaccines. We hypothesized that females would experience higher rates and grades of TRAEs. TRAE rates and grades were compared between sexes, with adjustment for multiple comparisons, and with mixed-effects models. Results: Multiple sex-related differences in TRAE rate and grade were observed in unadjusted comparisons, but only hyperglycemia and hypopigmentation were significantly higher-grade by sex after correcting for multiple comparisons: they were increased in males. In mixed-effect models, vaccination strategy, but not patient sex, was independently associated with TRAE rates and grades. Conclusions: These data do not support our hypothesis that TRAEs would be increased in females. Vaccine safety was supported for both males and females.