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

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 cytotox...

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Bibliographic Details
Published in:European journal of cancer (1990) 2017-09, Vol.82, p.56-65
Main Authors: Heppt, Markus V., Heinzerling, Lucie, Kähler, Katharina C., Forschner, Andrea, Kirchberger, Michael C., Loquai, Carmen, Meissner, Markus, Meier, Friedegund, Terheyden, Patrick, Schell, Beatrice, Herbst, Rudolf, Göppner, Daniela, Kiecker, Felix, Rafei-Shamsabadi, David, Haferkamp, Sebastian, Huber, Margit A., Utikal, Jochen, Ziemer, Mirjana, Bumeder, Irmgard, Pfeiffer, Christiane, Schäd, Susanne G., Schmid-Tannwald, Christoph, Tietze, Julia K., Eigentler, Thomas K., Berking, Carola
Format: Article
Language:English
Subjects:
Adult
Aged
Antibodies, Monoclonal - therapeutic use
Antibodies, Monoclonal, Humanized - therapeutic use
Antineoplastic Agents - therapeutic use
Apoptosis
Biomarker
Biomarkers, Tumor - analysis
Blood
C-reactive protein
C-Reactive Protein - analysis
Cell death
CTLA-4 Antigen - antagonists & inhibitors
CTLA-4 protein
Cytotoxicity
Eosinophils - cytology
Female
Health risks
Humans
Immune checkpoint
Immune checkpoint blockade
Immunotherapy
Immunotherapy - methods
Inhibition
Inhibitors
Ipilimumab
L-Lactate dehydrogenase
L-Lactate Dehydrogenase - blood
Lactate dehydrogenase
Lactic acid
Leukocytes (eosinophilic)
Lymphocytes T
Male
Malignancy
Medical prognosis
Melanoma
Melanoma - drug therapy
Melanoma - secondary
Metastases
Metastasis
Middle Aged
Monoclonal antibodies
Mortality
Multivariate analysis
Nivolumab
Parameter identification
Patients
PD-1 protein
Pembrolizumab
Prognosis
Programmed Cell Death 1 Receptor - antagonists & inhibitors
Proportional Hazards Models
Proteins
Regression Analysis
Retrospective Studies
Risk analysis
Risk factors
Serum levels
Skin cancer
Survival
Survival Analysis
Targeted cancer therapy
Uveal melanoma
Uveal Neoplasms - drug therapy
Uveal Neoplasms - secondary
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Summary: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 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. 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)
ISSN:0959-8049
1879-0852
DOI:10.1016/j.ejca.2017.05.038