Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies

Most adverse events with anti-programmed-cell-death protein 1 (PD-1)/PD-L1 agents are generally mild and reversible, yet some high-grade immune-related adverse events are managed with corticosteroids and other immune-modulating agents. The mechanisms underlying the development of these toxicities are the subject of ongoing studies.Immune checkpoint antibodies that augment the programmed cell death protein 1 (PD-1)/PD-L1 pathway have demonstrated antitumor activity across multiple malignancies, and gained recent regulatory approval as single-agent therapy for the treatment of metastatic malignant melanoma and nonsmall-cell lung cancer. Knowledge of toxicities associated with PD-1/PD-L1 blockade, as well as effective management algorithms for these toxicities, is pivotal in order to optimize clinical efficacy and safety. In this article, we review selected published and presented clinical studies investigating single-agent anti-PD-1/PD-L1 therapy and trials of combination approaches with other standard anticancer therapies, in multiple tumor types. We summarize the key adverse events reported in these studies and their management algorithms.