Ye W., Olsson-Brown A., Watson RA., Cheung VTF., Morgan RD., Nassiri I., Cooper R., Taylor CA., Akbani U., Brain O., Matin RN., Coupe N., Middleton MR., Coles M., Sacco JJ., Payne MJ., Fairfax BP.

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

Checkpoint-blocker-induced autoimmunity is associated with favourable outcome in metastatic melanoma and distinct T-cell expression profiles.

Ye W., Olsson-Brown A., Watson RA., Cheung VTF., Morgan RD., Nassiri I., Cooper R., Taylor CA., Akbani U., Brain O., Matin RN., Coupe N., Middleton MR., Coles M., Sacco JJ., Payne MJ., Fairfax BP.

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