BACKGROUND: Immune checkpoint blockers (ICBs) activate CD8+ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear. METHODS: Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab-sICB) or combination (nivolumab and ipilimumab-cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8+ T cells was sequenced and differential gene expression according to irAE development assessed. RESULTS: 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P
Journal article
Br J Cancer
05/2021
124
1661 - 1669
Aged, Aged, 80 and over, Antineoplastic Agents, Immunological, Autoimmune Diseases, Autoimmunity, CD8-Positive T-Lymphocytes, Female, Gene Expression Regulation, Neoplastic, Humans, Immune Checkpoint Inhibitors, Immunotherapy, Male, Melanoma, Middle Aged, Neoplasm Metastasis, Prognosis, Progression-Free Survival, Retrospective Studies, Skin Neoplasms, Survival Analysis, Transcriptome, Treatment Outcome, United Kingdom