Immune-Related Adverse Events and Therapeutic Outcomes After Stopping Immune Checkpoint Inhibitors due to Toxicity Among Patients With Metastatic Melanoma (University Hospitals Sussex).

Melanoma is an aggressive type of skin cancer. Immune checkpoint inhibitors (ICIs): pembrolizumab, ipilimumab and/or nivolumab are recommended for the treatment of metastatic melanoma. ICIs enhance the immune response by blocking PD-1 and/or CTLA-4, improving remission and overall survival (OS). However, ICIs can cause immune-related adverse events (irAEs) such as colitis and dermatitis. Recent studies have demonstrated association between irAEs and improved tumour regression. This study aimed to evaluate the relationship between OS and stopping ICIs therapy due to immunological toxicity in metastatic melanoma patients. This study was approved by The University Hospitals Sussex NHS Foundation Trust (UHSussex) (reference 1963) and the University of Brighton (reference 2024-12,878-Shamsaldeen). Data collected from files of patients diagnosed with metastatic melanoma treated with ICIs at UHSussex between October 2011 to December 2022. In a total of 344 metastatic melanoma patients, the OS was 41.3%. There were 184 patients (53.5%) experienced irAEs. Among 202 patients who died by the cut-off point, there were 115 (56.9%) patients who did not experience irAE, while 68.3% of the 142 patients who were alive experienced irAE revealing overall association (p < 0.001, Pearson's R = 0.249) with logistics regression analysis showed association between irAE and OS (p < 0.001). Kaplan-Meier survival analysis showed significant longer OS (p < 0.001) for patients experienced irAE. Stopping ICIs due to toxicity reported in 83 patients from which 56 patients were alive by the cut-off point (67.5%) revealing overall association (p < 0.001, Pearson's R = 0.171) with logistics regression analysis showed association between stopping ICI due to toxicity and OS (p < 0.001). Kaplan-Meier survival analysis showed significant longer OS (p = 0.027) in patients whom their ICI therapy was stopped due to immune-related toxicity. In conclusion, the positive correlation between irAEs and survival may highlight the potential value of irAEs and irAE-related toxicity as biomarkers for therapeutic efficacy in advanced melanoma management.