Abstract
BACKGROUND: Immune checkpoint blockade (ICB) has transformed cancer therapy, with long-term responses and a favorable safety profile; however, only a minority of patients respond. Response to ICB is influenced by immune-related genetic factors such as HLA haplotype, potentially including patient blood type and associated differences in diversity of the T-cell repertoire. A minority of patients experience immune-related adverse events (irAEs), with unclear relation to response or resistance. MATERIALS AND METHODS: In this single institution study, we aimed to investigate the relationship of time to treatment failure (TTF) with patient blood type and with occurrence of irAEs, among patients with metastatic cancer receiving ICB. RESULTS: We found a strong association of improved TTF with presence of irAEs, and also among patients with type O blood, compared with type A/B/AB blood. Among patients with type O blood, TTF was substantially longer among those experiencing an irAE (n = 44; adjusted HR 0.41, 95% CI 0.18,0.96). For patients with type A/B/AB blood, no significant association was present (n = 63; adjusted HR 0.69, 95% CI 0.39,1.21). For type O patients, median TTF of ICB was 13.4 months (95% CI: 3.79 months, NA) vs 2.55 months (95% CI: 1.95 months, 4.95 months) for other patients. CONCLUSION: This retrospective study of a cohort of patients receiving ICB suggests a preferential benefit among patients with type O blood and, in particular, among patients with type O blood who developed irAEs. Validation in future independent cohorts and investigation of a potential biologic basis for this finding is warranted.