Balancing Cancer Immunotherapy Efficacy and Toxicity

Anti–programmed cell death-1 receptor/programmed cell death-1 receptor ligand–directed therapies are transforming cancer care, with durable antitumor responses observed in multiple cancer types. Toxicities arising from therapy are autoimmune in nature and may affect essentially any organ system. The immunologic basis of such toxities is complex, with contributions from T-cell activation and autoantibody generation. Although less recognized, hypersensitivity reactions are also possible. Although most toxicities resolve with systemic corticosteroids, some require second-line immunosuppression. Furthermore, the safety of drug rechallenge is not well characterized, with variable rates of toxicity flares arising with re-exposure. Herein, we review toxicities of immune checkpoint inhibitor therapies, particularly focusing on issues that allergists/immunologists may clinically encounter, including interstitial nephritis, skin toxicity, and risks associated with immunotherapy rechallenge.