Comparative incidence and severity of immune-related adverse events among patients with melanoma on immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) are effective treatments for melanoma, but little is known regarding their comparative safety profiles. We conducted a retrospective study of immune-related adverse events (irAEs) among patients diagnosed with histopathologically-confirmed melanoma between 01/2010- 12/2021 treated with nivolumab, pembrolizumab, and/or ipilimumab. IrAEs were documented using CTCAE v5.0. Chi-squared, ANOVA, and multivariable logistic regression analyses were performed with adjustment for age, sex, ECOG, baseline lactate dehydrogenase, presence of metastasis, receipt of prior therapy. P-values were 2-tailed. Benjamini-Hochberg method was used for false-discovery rate correction with p ≤ .05 determining statistical significance. 672 patients were included. 66.8% were male with mean age at ICI initiation being 63.8 years. 70.5% experienced any-grade irAEs, while 28.6% experienced high- grade toxicity. 40.6% of patients had toxicity-related interruptions to their ICI regimen. Ipilimumab- nivolumab combination was associated with significantly higher rates of all-grade toxicity (P < 0.001) and high-grade toxicity (P < 0.001) than pembrolizumab. In comparing monotherapy regimens, ipilimumab was associated with significantly increased incidence of any-grade, but not high-grade, GI irAEs compared to pembrolizumab (P = 0.012). Among patients receiving PD-1 inhibitors, no significant differences were observed in incidences of all- and high-grade irAEs, rates of ICI regimen interruptions, and systemic treatment required for toxicities. This work highlights the comparative safety of nivolumab and pembrolizumab in treatment of melanoma. Additionally, while CTLA-4 inhibitors were associated with increased risk of GI toxicity, no significantly increased risk of endocrine and cutaneous toxicities were observed. Further investigation of ICIs’ comparative safety profiles in treatment of melanoma is warranted.