title: Autoimmune Bullous Skin Disorders with Immune Checkpoint Inhibitors Targeting PD-1 and PD-L1.
abstract: Monoclonal antibodies (mAb) targeting immune checkpoint pathways such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) may confer durable disease control in several malignancies. In some patients, immune checkpoint mAbs cause cutaneous immune-related adverse events. Although the most commonly reported cutaneous toxicities are mild, a subset may persist despite therapy and can lead to severe or life-threatening toxicity. Autoimmune blistering disorders are not commonly associated with immune checkpoint mAb therapy. We report a case series of patients who developed bullous pemphigoid (BP), an autoimmune process classically attributed to pathologic autoantibody formation and complement deposition. Three patients were identified. Two patients developed BP while receiving the anti-PD-1 mAb nivolumab, and one while receiving the anti-PD-L1 mAb durvalumab. The clinicopathologic features of each patient and rash, and corresponding radiologic findings at the development of the rash and after its treatment, are described. Patients receiving an anti-PD-1/PD-L1 mAb may develop immune-related BP. This may be related to both T-cell- and B-cell-mediated responses. Referral to a dermatologist for accurate diagnosis and management is recommended. Cancer Immunol Res; 4(5); 383-9. ©2016 AACR.
authors.affiliation: Department of Oncology, Sidney Kimmel Cancer Center at Johns Hopkins, Baltimore, Maryland. jnaidoo1@jhmi.edu.
authors.forename: Jarushka
authors.initials: J
authors.lastname: Naidoo
authors.affiliation: Department of Dermatology and Dermato-oncology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Katja
authors.initials: K
authors.lastname: Schindler
authors.affiliation: Department of Dermatology and Dermato-pathology, City of Hope Cancer Center and Beckman Research Institute, Duarte, California.
authors.forename: Christiane
authors.initials: C
authors.lastname: Querfeld
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Klaus
authors.initials: K
authors.lastname: Busam
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Jane
authors.initials: J
authors.lastname: Cunningham
authors.affiliation: Department of Medicine, Portland Providence Medical Center, Earl A. Chiles Research Institute, Portland, Oregon.
authors.forename: David B
authors.initials: DB
authors.lastname: Page
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Weill Cornell Medical College, New York, New York.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Postow
authors.affiliation: Department of Nursing, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Alyona
authors.initials: A
authors.lastname: Weinstein
authors.affiliation: Department of Nursing, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Anna Skripnik
authors.initials: AS
authors.lastname: Lucas
authors.affiliation: Department of Nursing, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Kathryn T
authors.initials: KT
authors.lastname: Ciccolini
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Weill Cornell Medical College, New York, New York. Department of Dermatology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Quigley
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Weill Cornell Medical College, New York, New York.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Lesokhin
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Weill Cornell Medical College, New York, New York.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Paik
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Weill Cornell Medical College, New York, New York.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Chaft
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Weill Cornell Medical College, New York, New York.
authors.forename: Neil H
authors.initials: NH
authors.lastname: Segal
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Weill Cornell Medical College, New York, New York.
authors.forename: Sandra P
authors.initials: SP
authors.lastname: D'Angelo
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Weill Cornell Medical College, New York, New York.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Dickson
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Weill Cornell Medical College, New York, New York. Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. Weill Cornell Medical College, New York, New York. Department of Dermatology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Mario E
authors.initials: ME
authors.lastname: Lacouture
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors*; D003875:Drug Eruptions / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000556:secondary; D000077594:Nivolumab; D010391:Pemphigoid, Bullous / Q000139:chemically induced* / Q000175:diagnosis / Q000473:pathology; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D014057:Tomography, X-Ray Computed
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; C000613593:durvalumab; D000077594:Nivolumab