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Association of Bullous Pemphigoid With Immune Checkpoint Inhibitor Therapy in Patients With CancerA Systematic Review

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Key Points

Question  What are common characteristics associated with immune checkpoint inhibitor–induced bullous pemphigoid (ICI-BP) in patients with cancer?

Findings  In this systematic review of 70 studies reporting data on 127 ICI-treated patients with cancer, ICI-BP was found to occur after all types of immunotherapy, including cytotoxic T lymphocyte–associated antigen inhibitors. Immunotherapy was discontinued for most patients after ICI-BP diagnosis, and common treatments included systemic and topical corticosteroids, followed by antibiotics, antihistamines, systemic immunomodulators, and biologics.

Meaning  This systematic review summarizes the literature base and published studies reporting the development of ICI-BP in patients with cancer; its results can potentially aid in informing disease-specific guidelines for affected patients.

Abstract

Importance  There is limited information on immune checkpoint inhibitor–induced bullous pemphigoid (ICI-BP) in patients with cancer, with most existing studies being case reports or small case series from a single institution. Prior review attempts have not approached the literature in a systematic manner and have focused only on ICI-BP secondary to anti–programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) therapy. The current knowledge base of all aspects of ICI-BP is limited.

Objective  To characterize the risk factors, clinical presentation, diagnostic findings, treatments, and outcomes of ICI-BP in patients with cancer as reported in the current literature.

Evidence Review  A systematic review was performed using PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Articles reporting data on individual patients who met preestablished inclusion criteria were selected, and a predefined set of data was abstracted. When possible, study results were quantitatively combined.

Findings  In total, 70 studies reporting data on 127 individual patients undergoing ICI therapy for cancer (median [IQR] age, 71 [64-77] years; 27 women [21.3%]) were included. In pooled analyses, patients ranged in age from 35 to 90 years. Immune checkpoint inhibitor–induced bullous pemphigoid often occurred during the course of anti-PD-1, PD-L1, or cytotoxic T lymphocyte–associated antigen 4 therapy but was also found to develop up to several months after treatment cessation. Prodromal symptoms, such as pruritus or nonspecific skin eruptions, were found in approximately half of the patient population. Histopathologic or serologic testing, when undertaken, was a helpful adjunct in establishing diagnosis. Treatment with immunotherapy was discontinued after ICI-BP development in most patients. The most common treatments were systemic and topical corticosteroids. Steroid-sparing therapies, such as antibiotics and other systemic immunomodulators, were also used as adjuvant treatment modalities. Biologic and targeted agents, used predominantly in cases refractory to treatment with corticosteroids, were associated with marked symptomatic improvement in most patients.

Conclusions and Relevance  The results of this systematic review suggest that ICI-BP often poses a therapeutic challenge for patients with cancer who are receiving immunotherapy. Further research on the early recognition, diagnosis, and use of targeted treatment modalities will be essential in developing more personalized treatment options for affected patients while minimizing morbidity and mortality.

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Article Information

Accepted for Publication: March 29, 2022.

Published Online: May 25, 2022. doi:10.1001/jamadermatol.2022.1624

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

Author Contributions: Ms Asdourian and Dr 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. Mss Asdourian and Shah contributed equally.

Concept and design: Asdourian, Shah, Reynolds, Chen.

Acquisition, analysis, or interpretation of data: Asdourian, Shah, Jacoby, Chen.

Drafting of the manuscript: Asdourian, Shah, Jacoby.

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

Statistical analysis: Asdourian, Shah.

Administrative, technical, or material support: Jacoby.

Supervision: Reynolds, Chen.

Conflict of Interest Disclosures: Dr Chen reported personal fees from Pfizer and Novartis outside the submitted work. 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 Melissa Lydston, MLS, Massachusetts General Hospital, for her assistance in designing the database search strategy. She was not compensated for her contributions.

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