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Management of Cutaneous Immune-Related Adverse Events in Patients With Cancer Treated With Immune Checkpoint InhibitorsA Systematic Review

Educational Objective
To learn the cutaneous eruptions that are associated with immune checkpoint inhibitor therapy.
1 Credit CME
Key Points

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.

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Article Information

Accepted for Publication: March 30, 2021.

Published Online: October 28, 2021. doi:10.1001/jamaoncol.2021.4318

Corresponding Author: Steven T. Chen, MD, MPH, MS-HPEd, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, 50 Staniford St, Ste 200, Boston, MA 02114 (stchen@partners.org).

Author Contributions: Drs Nadelmann and Chen had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Nadelmann and Yeh contributed equally to this work.

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: All authors.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Nadelmann.

Administrative, technical, or material support: Nadelmann, Chen.

Supervision: Yeh, Chen.

Conflict of Interest Disclosures: Dr Chen has received honoraria from Pfizer for serving on an advisory board for digital media. No other disclosures were reported.

Funding/Support: Dr Chen is supported by a Medical Dermatology Career Development Award from the Dermatology Foundation.

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank Kerry Reynolds, MD, Massachusetts General Hospital, for her work caring for patients with immune-related adverse events and for motivating this article. She was not compensated for her contributions.

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AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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