BackgroundMelanoma and the immune system are intimately related. However, the association of immunosuppressive medications (ISMs) with survival in melanoma is not well understood. The study evaluated this at a population level.MethodsA cohort of patients with a diagnosis of invasive cutaneous melanoma (2007–2015) was identified from the Ontario Cancer Registry and linked to identify demographics, stage at diagnosis, prescription of immunosuppressive medications (both before and after diagnosis), and outcomes. The demographics of patients with and without prescriptions for ISM were compared. Patients eligible for Ontario’s Drug Benefit Plan were included to ensure accurate prescription data. The primary outcome was overall survival. Cox Proportional Hazards Regression models identified factors associated with mortality, including use of ISM as a time-varying covariate.ResultsOf the 4954 patients with a diagnosis of cutaneous melanoma, 1601 had a prescription for ISM. The median age of the patients was 74 years. Overall, 58.4% of the patients were men (60.5% of those without ISM and 54% of those using ISM; p < 0.001). The use of oral immunosuppression was associated with an increased hazard of death (hazard ratio, 5.84; 95% confidence interval, 5.11–6.67; p < 0.0001) when control was used for age, disease stage at diagnosis, anatomic site, comorbidity, and treatment. Other factors associated with death were increasing age, male sex, increased disease stage, truncal location of primary melanoma, and inadequate treatment. In sensitivity analysis with steroid-only ISM use excluded, survival did not differ significantly (p = 0.355).ConclusionsThe use of immunosuppressive steroids for melanoma is associated with worse overall survival. Use of steroids should be limited when possible.