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Eur J Cancer. 2017 Apr;75:24-32. doi: 10.1016/j.ejca.2016.12.038. Epub 2017 Feb 16.

Programmed cell death protein-1 (PD-1) inhibitor therapy in patients with advanced melanoma and preexisting autoimmunity or ipilimumab-triggered autoimmunity.

Author information

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.

KEYWORDS:

Autoimmunity; Immune-related adverse events; Ipilimumab; Metastatic melanoma; Nivolumab; PD-1 inhibitor; Pembrolizumab

PMID:
28214654
DOI:
10.1016/j.ejca.2016.12.038
[Indexed for MEDLINE]

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