Ralf Gutzmer1, Anika Koop2, Friedegund Meier3, Jessica C Hassel4, Patrick Terheyden5, Lisa Zimmer6, Lucie Heinzerling7, Selma Ugurel8, Claudia Pföhler9, Anja Gesierich10, Elisabeth Livingstone11, Imke Satzger12, Katharina C Kähler13. 1. Skin Cancer Center Hannover, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany. Electronic address: Gutzmer.ralf@mh-hannover.de. 2. Skin Cancer Center Hannover, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany. Electronic address: Koop.anika@mh-hannover.de. 3. 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. 4. 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. 5. Department of Dermatology, University of Lübeck, Ratzeburger Allee 160, 23562 Luebeck, Germany. Electronic address: Patrick.terheyden@uksh.de. 6. Department of Dermatology, University of Duisburg-Essen, Essen, Germany. Electronic address: lisa.zimmer@uk-essen.de. 7. University Hospital Erlangen, Department of Dermatology, Erlangen, Germany. Electronic address: lucie.heinzerling@uk-erlangen.de. 8. Department of Dermatology, University of Duisburg-Essen, Essen, Germany. Electronic address: selma.ugurel@uk-essen.de. 9. Saarland University Medical School, Department of Dermatology, Homburg, Germany. Electronic address: Claudia.pfoehler@uks.eu. 10. University Hospital Würzburg, Department of Dermatology, Würzburg, Germany. Electronic address: gesierich_a@ukw.de. 11. Department of Dermatology, University of Duisburg-Essen, Essen, Germany. Electronic address: elisabeth.livingstone@uk.essen.de. 12. Skin Cancer Center Hannover, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany. Electronic address: Satzger.imke@mh-hannover.de. 13. Department of Dermatology, Skin Cancer Center, Schleswig-Holstein University Hospital, Campus Kiel, Kiel, Germany. Electronic address: kckaehler@yahoo.de.
Abstract
AIM: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
AIM: 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. PATIENTS AND METHODS: Metastatic melanomapatients 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. RESULTS: 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. CONCLUSION: 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: Lucie Heinzerling; Enrico N de Toni; Georg Schett; Gheorghe Hundorfean; Lisa Zimmer Journal: Dtsch Arztebl Int Date: 2019-02-22 Impact factor: 5.594
Authors: T Sakakida; T Ishikawa; Y Chihara; S Harita; J Uchino; Y Tabuchi; S Komori; J Asai; T Narukawa; A Arai; H Tsunezuka; T Kosuga; H Konishi; M Moriguchi; H Yasuda; F Hongo; M Inoue; S Hirano; O Ukimura; Y Itoh; T Taguchi; K Takayama Journal: Clin Transl Oncol Date: 2019-10-01 Impact factor: 3.405
Authors: Christopher S Nabel; Mariano Severgnini; Yin P Hung; Amy Cunningham-Bussel; Evisa Gjini; Katja Kleinsteuber; Lake J Seymour; Martha K Holland; Rachel Cunningham; Kristin D Felt; Marina Vivero; Scott J Rodig; Elena M Massarotti; Osama E Rahma; Lauren C Harshman Journal: Oncologist Date: 2019-05-14
Authors: Andrea Antonuzzo; Fabio Calabrò; Pietro Quaglino; Fausto Roila; Gian Domenico Sebastiani; Francesco Spina; Giuseppe Pasqualetti; Diego Cortinovis; Enrico Tagliaferri; Alessandro Peri; Elena Margherita Presotto; Maria Francesca Egidi; Luca Giacomelli; Ferruccio Farroni; Massimo Di Maio; Emmanuele De Luca; Marco Danova; Florian Scottè; Karin Jordan; Paolo Bossi Journal: Oncologist Date: 2020-03-17