The Real-World Safety Profile of Immune Checkpoint Inhibitors in Melanoma: FAERS Pharmacovigilance Analysis Complemented by Randomized Trial Evidence.

BACKGROUND AND AIMS: Melanoma can be effectively treated with immune checkpoint inhibitors (ICIs), but information regarding the risks of treatment-related adverse events (trAEs), immune-related adverse events (irAEs), and real-world adverse events (AEs) is scarce.

METHODS

We searched PubMed, Embase, Medline, and Cochrane CENTRAL databases for randomized controlled trials (RCTs) comparing ICIs for melanoma therapy up to February 16, 2025. Bayesian network meta-analysis (NMA) was conducted, and odds ratios (ORs) with 95% credible intervals (95%CrI) were calculated. A pharmacovigilance analysis was performed using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. ICI-associated AEs in patients with melanoma were obtained for the period from the first quarter (Q1) of 2004 to Q1 of 2023.

RESULTS

The NMA included 31 RCTs, comprising 11,937 patients with melanoma. Ipilimumab (Ipi), nivolumab (Nivo), and pembrolizumab (Pem) were ranked as having the lowest risk of any grade as well as grade 3-5 trAEs. Chemotherapy (Chemo) was associated with the lowest risk of any grade or grade 3-5 irAEs. Compared to other ICIs, Chemo, Ipi, and Ipi-Chemo were associated with the lowest risk of any irAEs. Based on the results of the FAERS pharmacovigilance analysis, we identified 5974 AEs in 4599 melanoma patients treated with ICIs. ICIs were associated with statistically significant indications involving 236 preferred terms (PTs). Thoroughly examined and pinpointed AEs were strongly correlated with ICIs. Pem treatment was associated with 166 significant PTs. Apart from malignant neoplasm progression and death, the most common PT was an immune-mediated adverse reaction.

CONCLUSION

The results of this study indicated that ICI safety profiles vary. These findings provide comparative safety signals that may help inform AE monitoring and risk assessment in patients with melanoma receiving ICIs, but they should not be interpreted as definitive prescribing guidance.