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Immune checkpoint inhibitors represent a paradigm change in the treatment of melanoma and other advanced cancers. These agents manipulate key immune-regulating pathways to restore immune responses against tumors. The success of this approach is demonstrated by ipilimumab (Yervoy®) for the treatment of advanced melanoma, with improvement in three-year survival rates of about 20%. Newer checkpoint inhibitors targeting the programmed death-1 (PD-1) pathway have been approved and may have higher response rates and improved tolerability.This article aims to educate nurses and increase their comfort level with these new therapies.The mechanism of action of immune checkpoint inhibitors is reviewed, and insight is provided on how nurses can use this knowledge to more effectively care for patients receiving these therapies.The use of immuno-oncology agents is increasing. Oncology nurses must understand the basic immune mechanism of action responsible for the novel toxicity profile characterized by immune-related adverse events (irAEs) and clinical response patterns. Managing irAEs with immune checkpoint inhibitors is not necessarily more difficult than with conventional agents, but a difference does exist. Nurses and other healthcare providers must consider the underlying cause of toxicity with immune checkpoint inhibitors when making management decisions.