Immune Checkpoint Inhibitor Toxicity

Abstract

Purpose of review: Immune checkpoint inhibitors have revolutionised the treatment of multiple malignancies and have a growing list of indications. As our familiarity with these agents grows, so does our understanding of their unique spectrum of toxicities. Here, we will review the literature regarding the toxicities of checkpoint inhibitors and address challenges encountered in day-to-day clinical practice.

Recent findings: Inhibitors of the PD-1/PD-L1 axis are considerably less toxic than the anti-CTLA-4 antibody ipilimumab. The combination of ipilimumab and anti-PD-1 agents is being trialled in multiple malignancies and is associated with increased toxicity. There is accumulating evidence suggesting a potential correlation between a subset of toxicities and clinical benefit in several tumour types, although conflicting data exists. Retrospective series have shown that anti-PD-1 can be safely administered to patients with prior high-grade toxicity from ipilimumab or combination immunotherapy. The management of checkpoint inhibitor toxicity is complex and requires collaboration with our subspecialty colleagues. Identifying predictive biomarkers of both efficacy and toxicity would likely help guide treatment decisions, and should be a research priority in the years ahead.

Keywords: CTLA-4; Checkpoint inhibitors; Immune-related adverse events (irAEs); Ipilimumab; Nivolumab; PD-1; Pembrolizumab; Toxicity.