Safety and efficacy of immune checkpoint inhibitors in patients with melanoma and pre-existing autoimmune conditions: a systematic review and meta-analysis

Abstract

Background Melanoma patients with pre-existing autoimmune diseases (AIDs) have been excluded from clinical trials of immune checkpoint inhibitors (ICIs), due to a risk of flare and immune-related adverse effects (irAEs). Materials and methods A comprehensive literature search of Medline, Embase, CINAHL and Scopus was carried out. Studies of melanoma patients with pre-existing AIDs were included. Two reviewers used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Outcomes assessed included all-grade and grade 3 or 4 de novo irAEs, AID flare, treatment discontinuation owing to adverse effect(s), treatment-related mortality and objective response rate (ORR). Results Thirty-two percent of patients with AIDs developed a flare, with 80% requiring immunosuppression. In patients with AIDs, meta-analysis revealed a higher risk of all-grade irAEs [risk ratio (RR) 1.16, 95% confidence interval (CI) 1.01-1.33, P = 0.0106] but not grade 3 or 4 (RR 1.21, 95% CI 0.99-1.47, P = 0.0663). Treatment discontinuation, treatment-related mortality and ORR were not different among patients with AIDs. Conclusions Melanoma patients with pre-existing AIDs are at significant risk of flare with ICI use. These patients had an increased risk of irAEs of any grade. Although there was a trend towards increased risk of severe irAEs, this was not statistically significant. irAEs did not result in treatment-related deaths, and there were no differences in treatment response. Risks should be discussed, coupled with close monitoring. c 2025 The Author(s).