Question
What are the most effective treatments for each subtype of cutaneous adverse events associated with immune checkpoint inhibitor therapy?
Findings
In this systematic review, common treatment strategies included topical corticosteroids and systemic immunomodulators, including oral/intravenous corticosteroids, antimetabolite agents, calcineurin inhibitors, and tumor necrosis factor–α inhibitors, as well as systemic antipruritics for symptomatic relief.
Meaning
The study findings build on recent literature by providing a systematic review of all published studies since the advent of immunotherapy and describing reported novel treatments of dermatologic adverse events, potentially becoming instrumental in creating new guidelines for clinicians to tailor the treatment and management of these events.
Importance
There exists a paucity of literature that summarizes the effective management of cutaneous immune-related adverse events (cirAEs) in patients with cancer who are receiving immune checkpoint inhibitors (ICIs). Most published articles are small case series from a single institution. To our knowledge, the spectrum of possible treatments has not been systematically reviewed to highlight the breadth of options when caring for patients with cirAEs.
Objective
To further characterize the development of subtypes of cirAEs in patients with cancer treated with ICIs and provide recommendations on optimal treatment regimens based on the current literature.
Evidence Review
A search was performed in PubMed, Embase European, Web of Science, and Google Scholar on June 26, 2020, according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines, limited to the years 2010 to 2020. Articles that met predetermined inclusion criteria (published between January 1, 2010, and June 1, 2020; written in the English language; and original articles, brief reports, case reports, and research letters that reported primarily on cirAE management) were selected, and data were abstracted. Articles that met the scope of the review were also added from reference lists. When possible, the results of studies that addressed a similar question were combined quantitatively.
Findings
In total, 138 studies (87 from the aforementioned literature search and 51 additional studies pulled from the reference lists of included articles) were included that reported on 879 cirAEs. The subtypes of cirAEs included maculopapular, pruritus, lichenoid, immunobullous, psoriasiform, granulomatous, erythema multiforme or Stevens Johnson Syndrome, drug rash with eosinophilia and systemic symptoms, connective tissue disease, hair, oral, and miscellaneous. Treatments for cirAEs included a combination of topical corticosteroids, systemic corticosteroids, steroid-sparing agents, and discontinuation or cessation of immunotherapy.
Conclusions and Relevance
This systematic review found that treatment with ICIs was associated with many types of skin toxic effects, each with unique treatment options beyond current published guidelines. Further research into key differences between subtypes is critical to improve the care provided to patients with cancer.