title: Programmed cell death protein-1 (PD-1) inhibitor therapy in patients with advanced melanoma and preexisting autoimmunity or ipilimumab-triggered autoimmunity.
abstract: Programmed cell death protein 1 (PD-1) inhibitors are a common treatment strategy for metastatic melanoma and other tumour entities. Clinical trials usually exclude patients with preexisting autoimmune diseases, thus experience with PD-1 inhibitor (PD-1i) in this patient population is limited.
  
  
  
  Metastatic melanoma patients with preexisting autoimmune disorders or previous ipilimumab-triggered immune-related adverse events (irAE) undergoing treatment with PD-1i from seven German skin cancer centres were evaluated retrospectively with regard to flare of the preexisting autoimmunity and development of new, not preexisting irAE as well as response to PD-1i therapy.
  
  
  
  In total, 41 patients had either preexisting autoimmunity (n=19, group A, including two patients with additional ipilimumab-triggered autoimmune colitis) or ipilimumab-triggered irAE (n=22, group B). At PD-1i therapy initiation, six patients in group A and two patients in group B required immunosuppressive therapy. In group A, a flare of preexisting autoimmune disorders was seen in 42% of patients, new irAE in 16%. In group B, 4.5% of patients showed a flare of ipilimumab-triggered irAE and 23% new irAE. All flares of preexisting autoimmune disorders or irAE were managed by immunosuppressive and/or symptomatic therapy and did not require termination of PD-1i therapy. tumour responses (32% in group A and 45% in group B) were unrelated to occurrence of autoimmunity.
  
  
  
  While preexisting autoimmunity commonly showed a flare during PD-1i therapy, a flare of ipilimumab-triggered irAE was rare. Response rates were above 30% and unrelated to irAE. PD-1i therapy can be considered in patients with autoimmune disorders depending on severity and activity of autoimmunity.
authors.affiliation: Skin Cancer Center Hannover, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany. Electronic address: Gutzmer.ralf@mh-hannover.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gutzmer
authors.affiliation: Skin Cancer Center Hannover, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany. Electronic address: Koop.anika@mh-hannover.de.
authors.forename: Anika
authors.initials: A
authors.lastname: Koop
authors.affiliation: Department of Dermatology and National Center for Tumor Diseases, University Hospital Carl Gustav at the TU Dresden, Fetscherstr. 74, 01307, Dresden, Germany. Electronic address: Friedegund.meier@uniklinikum-dresden.de.
authors.forename: Friedegund
authors.initials: F
authors.lastname: Meier
authors.affiliation: Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany. Electronic address: Jessica.hassel@med.uni-heidelberg.de.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Hassel
authors.affiliation: Department of Dermatology, University of Lübeck, Ratzeburger Allee 160, 23562 Luebeck, Germany. Electronic address: Patrick.terheyden@uksh.de.
authors.forename: Patrick
authors.initials: P
authors.lastname: Terheyden
authors.affiliation: Department of Dermatology, University of Duisburg-Essen, Essen, Germany. Electronic address: lisa.zimmer@uk-essen.de.
authors.forename: Lisa
authors.initials: L
authors.lastname: Zimmer
authors.affiliation: University Hospital Erlangen, Department of Dermatology, Erlangen, Germany. Electronic address: lucie.heinzerling@uk-erlangen.de.
authors.forename: Lucie
authors.initials: L
authors.lastname: Heinzerling
authors.affiliation: Department of Dermatology, University of Duisburg-Essen, Essen, Germany. Electronic address: selma.ugurel@uk-essen.de.
authors.forename: Selma
authors.initials: S
authors.lastname: Ugurel
authors.affiliation: Saarland University Medical School, Department of Dermatology, Homburg, Germany. Electronic address: Claudia.pfoehler@uks.eu.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pföhler
authors.affiliation: University Hospital Würzburg, Department of Dermatology, Würzburg, Germany. Electronic address: gesierich_a@ukw.de.
authors.forename: Anja
authors.initials: A
authors.lastname: Gesierich
authors.affiliation: Department of Dermatology, University of Duisburg-Essen, Essen, Germany. Electronic address: elisabeth.livingstone@uk.essen.de.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Livingstone
authors.affiliation: Skin Cancer Center Hannover, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany. Electronic address: Satzger.imke@mh-hannover.de.
authors.forename: Imke
authors.initials: I
authors.lastname: Satzger
authors.affiliation: Department of Dermatology, Skin Cancer Center, Schleswig-Holstein University Hospital, Campus Kiel, Kiel, Germany. Electronic address: kckaehler@yahoo.de.
authors.forename: Katharina C
authors.initials: KC
authors.lastname: Kähler
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D012008:Recurrence; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D000074324:Ipilimumab; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; C582435:pembrolizumab
keywords: Autoimmunity; Immune-related adverse events; Ipilimumab; Metastatic melanoma; Nivolumab; PD-1 inhibitor; Pembrolizumab