4.5 Article

Prognostic biomarkers for immunotherapy with ipilimumab in metastatic melanoma

期刊

CLINICAL AND EXPERIMENTAL IMMUNOLOGY
卷 197, 期 1, 页码 74-82

出版社

WILEY
DOI: 10.1111/cei.13283

关键词

anti-CTLA-4; endostatin; Gal3BP; immunotherapy; melanoma

资金

  1. Department of Health, Oslo, Norway [NCT0268196/EudraCT 2013-002408-2015]
  2. Cancer Clinic, Oslo University Hospital through the Metaflammation Strategic Focus Area
  3. Bodil and Magnes Foundation

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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 1standard deviation increase in endostatin gave 174 times [95% confidence interval (CI)=110-278, P=0019] and for Gal3BP 152 times (95% CI=101-229, P=0047) 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.

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