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Eur J Cancer. 2017 Sep;82:56-65. doi: 10.1016/j.ejca.2017.05.038. Epub 2017 Jun 22.

Prognostic factors and outcomes in metastatic uveal melanoma treated with programmed cell death-1 or combined PD-1/cytotoxic T-lymphocyte antigen-4 inhibition.

Author information

1
Department of Dermatology and Allergy, University Hospital Munich (LMU), Frauenlobstr. 9-11, 80337 Munich, Germany. Electronic address: Markus.Heppt@med.uni-muenchen.de.
2
Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, Germany. Electronic address: Lucie.Heinzerling@uk-erlangen.de.
3
Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Str. 7, 24105 Kiel, Germany. Electronic address: kkaehler@dermatology.uni-kiel.de.
4
Department of Dermatology, Center for Dermatooncology, University Hospital Tübingen, Liebermeisterstr. 25, 72076 Tübingen, Germany. Electronic address: andrea.forschner@med.uni-tuebingen.de.
5
Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054 Erlangen, Germany. Electronic address: Michael.Kirchberger@uk-erlangen.de.
6
Department of Dermatology, University Medical Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. Electronic address: Carmen.Loquai@unimedizin-mainz.de.
7
Department of Dermatology, Venereology and Allergology, Goethe University, Theodor-Stern Kai 7, 60590 Frankfurt am Main, Germany. Electronic address: Markus.Meissner@kgu.de.
8
Department of Dermatology, Skin Cancer Center, National Center for Tumor Diseases, Medical Faculty and University Hospital Carl Gustav Carus, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany. Electronic address: Friedegund.Meier@uniklinikum-dresden.de.
9
Department of Dermatology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. Electronic address: Patrick.Terheyden@uksh.de.
10
Department of Dermatology, SRH Wald-Klinikum Gera GmbH, Str. des Friedens 122, 07548 Gera, Germany. Electronic address: Beatrice.Schell@wkg.srh.de.
11
HELIOS Skin Cancer Center Erfurt, HELIOS Clinic Erfurt, Nordhäuser Str. 74, 99089 Erfurt, Germany. Electronic address: rudolf.herbst@helios-kliniken.de.
12
Department of Dermatology and Allergology, Justus Liebig University, University Medical Center Gießen and Marburg, Gaffkystr. 14, 35392 Gießen, Germany. Electronic address: Daniela.Goeppner@med.ovgu.de.
13
Department of Dermatology and Allergy, Skin Cancer Center, Charité Universitätsmedizin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: felix.kiecker@charite.de.
14
Department of Dermatology, Medical Center - University of Freiburg, Hauptstr. 7, 79104 Freiburg, Germany. Electronic address: david.rafei-shamsabadi@uniklinik-freiburg.de.
15
Department of Dermatology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany. Electronic address: Sebastian.Haferkamp@klinik.uni-regensburg.de.
16
Department of Dermatology and Allergic Diseases, Ulm University, Albert-Einstein-Allee 23, 89081 Ulm, Germany. Electronic address: margit.huber@uniklinik-ulm.de.
17
Skin Cancer Unit, German Cancer Research Center (DKFZ) and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. Electronic address: Jochen.Utikal@umm.de.
18
Department of Dermatology, Venereology, and Allergology, University Hospital Leipzig, Philipp-Rosenthal-Str. 23, 04103 Leipzig, Germany. Electronic address: Mirjana.Ziemer@medizin.uni-leipzig.de.
19
Clinic of Internal Medicine, University Hospital Munich (LMU), Ziemssenstr. 1, 80336 Munich, Germany. Electronic address: praxis@onkologie-ebersberg.de.
20
Department of Dermatology, Klinikum Augsburg, Sauerbruchstr. 6, 86179 Augsburg, Germany. Electronic address: Christiane.Pfeiffer@klinikum-augsburg.de.
21
Department of Dermatology and Venereology, University Medical Center Rostock, Strempelstr.13, 18057 Rostock, Germany. Electronic address: susanne.schaed@uni-rostock.de.
22
Institute for Clinical Radiology, University Hospital Munich (LMU), Ziemssenstr. 1, 80336 Munich, Germany. Electronic address: Christoph.Schmid-Tannwald@med.uni-muenchen.de.
23
Department of Dermatology and Allergy, University Hospital Munich (LMU), Frauenlobstr. 9-11, 80337 Munich, Germany. Electronic address: Julia.Tietze@med.uni-muenchen.de.
24
Department of Dermatology, Center for Dermatooncology, University Hospital Tübingen, Liebermeisterstr. 25, 72076 Tübingen, Germany. Electronic address: thomas.eigentler@med.uni-tuebingen.de.
25
Department of Dermatology and Allergy, University Hospital Munich (LMU), Frauenlobstr. 9-11, 80337 Munich, Germany. Electronic address: Carola.Berking@med.uni-muenchen.de.

Abstract

BACKGROUND:

Uveal melanoma (UM) is an ocular malignancy with high potential for metastatic spread. In contrast to cutaneous melanoma, immunotherapy has not yet shown convincing efficacy in patients with UM. Combined immune checkpoint blockade with checkpoint programmed cell death-1 (PD-1) and checkpoint cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibition has not been systematically assessed for UM to date.

PATIENTS AND METHODS:

Patients with metastatic UM treated with either PD-1 inhibitor monotherapy or combined PD-1 inhibitor and ipilimumab (an anti-CTLA-4 monoclonal antibody) were included from 20 German skin cancer centres. Records from 96 cases were analysed for treatment outcomes. Clinical and blood parameters associated with overall survival (OS) or treatment response were identified with multivariate Cox regression and binary logistic regression.

RESULTS:

Eighty-six patients were treated with PD-1 inhibitors only (n = 54 for pembrolizumab, n = 32 for nivolumab) with a centrally confirmed response rate of 4.7%. Median OS was 14 months for pembrolizumab-treated and 10 months for nivolumab-treated patients (p = 0.765). Fifteen patients were treated with combined immune checkpoint blockade with partial response observed in two cases. Median OS was not reached in this group. Multivariate Cox regression identified Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.002), elevated serum levels of lactate dehydrogenase (LDH) (p = 0.002) and C-reactive protein (CRP) (p = 0.001), and a relative eosinophil count (REC) <1.5% (p = 0.002) as independent risk factors for poor survival. Patients with elevated CRP and LDH and a REC <1.5% were at highest risk for disease progression and death (p = 0.001).

CONCLUSIONS:

Blood markers predict survival in metastatic UM treated with immune checkpoint blockade. Normal serum levels of LDH and CRP and a high REC may help identify patients with better prognosis.

KEYWORDS:

Biomarker; Immune checkpoint blockade; Ipilimumab; Nivolumab; Pembrolizumab; Uveal melanoma

PMID:
28648699
DOI:
10.1016/j.ejca.2017.05.038
[Indexed for MEDLINE]

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