A Review and Comparison of Immune-Checkpoint Inhibitors in the Treatment of Metastatic Uveal Melanoma

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Introduction: Metastatic uveal melanoma (mUM) is a rare and aggressive malignancy characterised by poor responsiveness to conventional chemotherapies, posing significant treatment challenges. Immune checkpoint inhibitor (ICI) therapies, including monotherapies with Ipilimumab, pembrolizumab, and nivolumab, as well as dual ICI therapy, have emerged as potential treatments. Whilst current research favours dual therapy over single therapy, comprehensive individualised comparisons of the efficacy and safety profiles of these therapies remain limited. This meta-analysis aims to evaluate the clinical outcomes of single ICI therapies individually and compare against combination therapy to guide optimal treatment strategies for mUM. Methods: A systematic literature review was conducted to identify studies reporting objective response rates (ORR), disease control rates (DCR), median progression-free survival (MPFS), and adverse event rates (AER) for Ipilimumab, pembrolizumab, nivolumab, and dual ICI therapy. Data were aggregated using forest plots and analysed to compare the efficacy and safety of each regimen. Results: Dual ICI therapy demonstrated the highest ORR and DCR but showed no statistically significant advantage over monotherapies. Dual therapy also had a lower MPFS than both pembrolizumab and nivolumab monotherapies. Furthermore, dual therapy was associated with a much greater AER compared to any single therapy, including pembrolizumab and nivolumab. Conclusions: While dual ICI therapy offers improved ORR and DCR on aggregate analyses, monotherapies like pembrolizumab provide comparable outcomes in specific metrics, particularly MPFS, with significantly reduced toxicity. These findings underscore the need for personalised ICI regimens tailored to individual patient profiles rather than defaulting to dual therapy. Further research is essential to refine treatment guidelines and optimise outcomes for mUM patients.