Heppt, Markus V. and Heinzerling, Lucie and Kaehler, Katharina C. and Forschner, Andrea and Kirchberger, Michael C. and Loquai, Carmen and Meissner, Markus and Meier, Friedegund and Terheyden, Patrick and Schell, Beatrice and Herbst, Rudolf and Goeppner, Daniela and Kiecker, Felix and Rafei-Shamsabadi, David and Haferkamp, Sebastian and Huber, Margit A. and Utikal, Jochen and Ziemer, Mirjana and Bumeder, Irmgard and Pfeiffer, Christiane and Schaed, Susanne G. and Schmid-Tannwald, Christoph and Tietze, Julia K. and Eigentler, Thomas K. and Berking, Carola (2017) Prognostic factors and outcomes in metastatic uveal melanoma treated with programmed cell death-1 or combined PD-1/cytotoxic T-lymphocyte antigen-4 inhibition. EUROPEAN JOURNAL OF CANCER, 82. pp. 56-65. ISSN 0959-8049, 1879-0852
Full text not available from this repository. (Request a copy)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. (C) 2017 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | C-REACTIVE PROTEIN; UNTREATED MELANOMA; IPILIMUMAB; NIVOLUMAB; CANCER; PEMBROLIZUMAB; MUTATIONS; GENES; Ipilimumab; Pembrolizumab; Nivolumab; Immune checkpoint blockade; Uveal melanoma; Biomarker |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:15 |
| Last Modified: | 15 Feb 2019 08:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1345 |
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