Impact of the development of immune related adverse events in metastatic melanoma treated with PD -1 inhibitors

Abstract

Some clinical trials have described improved outcomes in patients who develop immune-related adverse events (irAEs) while receiving immune checkpoint inhibitors for advanced melanoma. It is unknown if this effect would be seen in a real-world population. This is a single-center retrospective analysis of all patients receiving single-agent PD-1 inhibitor for unresectable stage III or stage IV melanoma between 2012 and 2018. The majority of patients had cutaneous melanoma and were elderly (put in median and range). Totally 33.3% were BRAF mutated and 66.7% had PD-1 inhibitor as first-line treatment for metastatic disease. Also, 22% of patients had brain metastases at presentation. Of the 87 patients included in this analysis, 48 (55%) developed at least one irAE. Dermatologic toxicities were the most common irAE. The median time to develop any irAE was 12 weeks. Only one patient died of immune-related toxicity. Overall survival in the population of patients that had an irAE was significantly greater than those that did not have any toxicity (21.1 vs. 7.5 months; P < 0.001). The development of endocrine toxicity had the strongest correlation with survival as did patient with grade 1 (NCI V.5) toxicity. The development of multiple toxicities did not correlate with survival. In patients with multiple toxicities, the type of irAE that presented initially did not impact the outcome. These findings add to the growing body of literature suggesting an association between irAEs and immune-checkpoint inhibitor efficacy while suggesting that this benefit may depend on the type of toxicity and severity.