Immune checkpoint inhibitors, endocrine adverse events, and outcomes of melanoma.

Objective: Immune checkpoint inhibitors (ICI) can cause endocrine adverse events. However, endocrine adverse events (AEs). However, endocrine AEs could be related to better treatment outcomes. Our aim was to investigate whether this holds true in a real-world setting of metastatic melanoma patients. Design: A retrospective single-institution study. Methods: We included 140 consecutive metastatic melanoma patients treated with ICI between January 2012 and May 2019. We assessed the endocrine toxicity and the best possible treatment outcomes from electronic patient records, including laboratory parameters and radiological images. Results: Of the treated patients, 21 patients (15%) were treated with ipilimumab, 46 (33%) with nivolumab, 67 (48%) with pembrolizumab, and 6 (4%) with combination therapy (ipilimumab + nivolumab). Endocrine AEs appeared in 29% (41/140) patients. Three patients had two different endocrine AEs. Thyroid disorders were the most common: 26% (36/140), followed by hypophysitis: 4% (5/140). Three subjects (2%, 3/140) were diagnosed with autoimmune diabetes. Three patients had to terminate treatment due to endocrine toxicity. Radiological manifestations of endocrine AEs were found in 16 patients (39%, 16/41). Endocrine toxicity was associated with significantly better treatment outcomes. Median progression-free survival (8.1 months, range 5.1-11.1 months vs 2.7 months, range 2.4-3.0 months, P < 0.001), and median overall survival (47.5 months, range 15.5-79.5 months vs 23.7 months, range 15.3-32.1 months, P = 0.035) were longer for patients experiencing endocrine AEs. Conclusions: The higher number of endocrine AEs suggest that regular laboratory monitoring aids in AE detection. Endocrine AEs in metastatic melanoma may correlate with better treatment outcomes.