Associations between immune-related adverse events and the effectiveness of immunotherapeutic agents in advanced melanoma: A systematic review and meta-analysis

Abstract

Background: In contrast to conventional chemotherapy, the use of immune checkpoint inhibitors (ICIs) can occasionally result in distinct toxic effects that are reminiscent of autoimmune disorders. This effect is known as an immune-related adverse event (irAE). Achieving maximum therapeutic efficacy with ICIs requires careful balancing of antitumor immunity and autoimmunity. Moreover, studies on patients with metastatic melanoma have revealed a correlation between adverse events and the clinical outcomes of ICIs. Ongoing research is aimed at determining whether the occurrence of irAEs is associated with clinical efficacy in patients with metastatic melanoma. However, the results of current studies investigating the correlation between antitumor efficacy and the development of irAEs have been inconsistent. Objectives: This study aimed to reveal a robust correlation between irAEs and clinical outcomes in patients with metastatic melanoma. Methods: Electronic databases, including PubMed, Web of Science, and the Cochrane Library, were comprehensively searched from their inception to September 2023. The primary and secondary outcomes were effectiveness and toxicity, respectively. Results: We retrospectively analyzed 26 nonrandomized controlled trials involving 6263 patients. Twenty-six studies revealed that irAEs were significantly associated with improved progression-free survival (P = 0.0001) and overall survival (P < 0.00001). Conclusion: Our study demonstrated that the incidence of irAEs represents a potential, though not robust, predictor of survival outcomes among patients afflicted with advanced melanoma undergoing treatment with various ICIs. The specific subtypes of irAEs require further investigation.

Keywords

• immune checkpoint inhibitors
• immune-related adverse events
• survival
• trial-based meta-analysis