Prognostic biomarkers for immunotherapy with ipilimumab in metastatic melanoma.

Autor: Nyakas M; Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Aamdal E; Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Jacobsen KD; Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway., Guren TK; Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway., Aamdal S; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Hagene KT; Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway., Brunsvig P; Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway., Yndestad A; Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway., Halvorsen B; Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway., Tasken KA; Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Aukrust P; Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway.; K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway.; K. G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway., Maelandsmo GM; Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.; Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway., Ueland T; Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; K. G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway.
Jazyk: angličtina
Zdroj: Clinical and experimental immunology [Clin Exp Immunol] 2019 Jul; Vol. 197 (1), pp. 74-82. Date of Electronic Publication: 2019 Mar 21.
DOI: 10.1111/cei.13283
Abstrakt: New therapies, including the anti-cytotoxic T lymphocyte antigen (CTLA)-4 antibody, ipilimumab, is approved for metastatic melanoma. Prognostic biomarkers need to be identified, because the treatment has serious side effects. Serum samples were obtained before and during treatment from 56 patients with metastatic or unresectable malignant melanoma, receiving treatment with ipilimumab in a national Phase IV study (NCT0268196). Expression of a panel of 17 inflammatory-related markers reflecting different pathways including extracellular matrix remodeling and fibrosis, vascular inflammation and monocyte/macrophage activation were measured at baseline and the second and/or third course of treatment with ipilimumab. Six candidate proteins [endostatin, osteoprotegerin (OPG), C-reactive protein (CRP), pulmonary and activation-regulated chemokine (PARC), growth differentiation factor 15 (GDF15) and galectin-3 binding-protein (Gal3BP)] were persistently higher in non-survivors. In particular, high Gal3BP and endostatin levels were also independently associated with poor 2-year survival after adjusting for lactate dehydrogenase, M-stage and number of organs affected. A 1 standard deviation increase in endostatin gave 1·74 times [95% confidence interval (CI) = 1·10-2·78, P = 0·019] and for Gal3BP 1·52 times (95% CI = 1·01-2·29, P = 0·047) higher risk of death in the adjusted model. Endostatin and Gal3BP may represent prognostic biomarkers for patients on ipilimumab treatment in metastatic melanoma and should be further evaluated. Owing to the non-placebo design, we could only relate our findings to prognosis during ipilimumab treatment.
(© 2019 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.)
Databáze: MEDLINE
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