Bullous Pemphigoid Induced by antiPD-1/PDL-1 Therapy

Overview

Immune checkpoint inhibitors (monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD- L1)) have revolutionized the treatment of many cancers. The widespread use of these treatments has triggered a new spectrum of immune related adverse events (irAE). Several cases of bullous pemphigoid (BP) triggered by antiPD-1/PDL-1 therapy have been reported, and their characteristics are currently poorly described in the literature. The investigators sought to collect the French cases of BP triggered by antiPD-1/PDL-1 therapy, and to describe their clinical, biological and histological characteristics. In this national, retrospective, observational study, investigators included patients treated with antiPD-1/PDL-1 therapy, with a diagnosis of bullous pemphigoid occurring during treatment or up to 12 months after its discontinuation. Diagnosis of BP was made by the dermatologist and was based on the following criteria: compatible clinical presentation, compatible histopathology findings, positive direct immunofluorescence (DIF) studies, positive enzyme-linked immunosorbent assay BP180/enzyme-linked immunosorbent assay BP230.

All members of French study Group on Autoimmune Bullous Skin Diseases and French group of Onco-dermatology were asked to report cases of bullous pemphigoid induced by antiPD-1/PDL-1 therapy from 2014 to 2019. In this retrospective, observational cohort study, investigators included patients treated with PD-1 or PD-L1 inhibitor, with a diagnosis of bullous pemphigoid occurring during treatment or up to 12 months after its discontinuation. Diagnosis of BP was made by the dermatologist and was based on the following criteria developed by the French Bullous Study Group : compatible clinical presentation (absence of atrophic scars, absence of mucosal involvement and absence of predominant bullous lesions on the neck and head), compatible histopathology findings (subepidermal blister on skin biopsy; and linear deposits of IgG and C3 along the basement-membrane zone), positive DIF studies, positive enzyme-linked immunosorbent assay BP180/enzyme-linked immunosorbent assay BP230. For each case, collected data were : sex, type of tumor, type of checkpoint inhibitor, age at the onset of the checkpoint inhibitor, time from the onset of BP compared to the onset of the PD-1 inhibitor, clinical presentation of BP, results of complementary exams (skin biopsies, enzyme-linked immunosorbent assay for BP180 and BP230 and indirect immunofluorescence studies if available); treatment of BP used, consequence on antiPD-1/PD-L1 therapy, course of the tumor, other irAEs. Overall tumor response was determined by the treating oncologist and classified using RECIST 1.1 (Response Evaluation Criteria in Solid Tumors).