Adverse cutaneous toxicities by PD-1/PD-L1 immune checkpoint inhibitors: pathogenesis, treatment, and surveillance

Abstract

Introduction The therapeutic use of humanised monoclonal programmed cell death 1 (PD-1) (pembrolizumab, and nivolumab) and programmed cell death ligand-1 (PD-L1) (atezolizumab, avelumab, durvalumab) immune checkpoint inhibitors (ICPi) as potent anticancer therapies is rapidly increasing. The mechanism of signalling of anti-PD-1/PD-L1 involves triggering cytotoxic CD4+/CD8 + T cell activation and subsequent abolition of cancer cells which induces specific immunologic adverse events that are specific to these therapies. These drugs can cause numerous cutaneous reactions and are characterized as the most frequent immune-related adverse events (irAEs). Majority of cutaneous irAEs range from non-specific eruptions to detectible skin manifestations, which may be self-limiting and present acceptable skin toxicity profiles, while some may produce life-threatening complications. Objective This review aims to illuminate the associated cutaneous irAEs related to drugs used in oncology along with the relevant mechanism(s) and management. Areas covered Literature was searched using various databases including Pub-Med, Google Scholar, and Medline. The search mainly involved research articles, retrospective studies, case reports, and clinicopathological findings. With this review article, an overview of the cutaneous irAEs with anti-PD-1/PD-L1 therapy, as well as suggestions, have been provided, so that their recognition at early stages could help in better management and would prevent treatment discontinuation. HIGHLIGHTS Cutaneous adverse effects are the most prevalent immune-related adverse events induced by anti-PD-1/PD-L1 immune-checkpoint antibodies. Cutaneous toxicities mainly manifest in the form of maculopapular rash and pruritus. More specific cutaneous complications can also occur, including vitiligo, worsened psoriasis, lichenoid dermatitis, mucosal involvement (e.g. oral lichenoid reaction), dermatomyositis, lupus erythematosus. Cutaneous manifestations can be life-threatening including Stevens-Johnson syndrome/toxic epidermal necrolysis (TEN). Dermatologic toxicities are usually mild, readily manageable, and rarely result in significant morbidity. Adequate management of the cutaneous adverse event and recognition in early stages could lead to the prevention of worsening of the lesions and limit treatment disruption.