Baseline Peripheral Blood Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated with Ipilimumab
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- Alexander Martens
- 1Department of Dermatology, University Medical Center, Tübingen, Germany.
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- Kilian Wistuba-Hamprecht
- 1Department of Dermatology, University Medical Center, Tübingen, Germany.
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- Marnix Geukes Foppen
- 3The Netherlands Cancer Institute, Amsterdam, the Netherlands.
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- Jianda Yuan
- 4Memorial Sloan Kettering Cancer Center, New York, New York.
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- Michael A. Postow
- 4Memorial Sloan Kettering Cancer Center, New York, New York.
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- Phillip Wong
- 4Memorial Sloan Kettering Cancer Center, New York, New York.
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- Emanuela Romano
- 6Department of Oncology, Service of Medical Oncology, Research Unit 932, Institut Curie, Paris, France.
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- Amir Khammari
- 7Department of Oncodermatology, INSERM Research Unit 892, University Hospital, Nantes, France.
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- Brigitte Dreno
- 7Department of Oncodermatology, INSERM Research Unit 892, University Hospital, Nantes, France.
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- Mariaelena Capone
- 8Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy.
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- Paolo A. Ascierto
- 8Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy.
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- Anna Maria Di Giacomo
- 9Division of Medical Oncology and Immunotherapy, University Hospital of Siena, Italy.
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- Michele Maio
- 9Division of Medical Oncology and Immunotherapy, University Hospital of Siena, Italy.
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- Bastian Schilling
- 10Department of Dermatology, University Hospital, West German Cancer Center, University Duisburg-Essen, Essen, Germany.
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- Antje Sucker
- 10Department of Dermatology, University Hospital, West German Cancer Center, University Duisburg-Essen, Essen, Germany.
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- Dirk Schadendorf
- 10Department of Dermatology, University Hospital, West German Cancer Center, University Duisburg-Essen, Essen, Germany.
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- Jessica C. Hassel
- 11German Cancer Consortium (DKTK), Heidelberg, Germany.
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- Thomas K. Eigentler
- 1Department of Dermatology, University Medical Center, Tübingen, Germany.
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- Peter Martus
- 13Departments of Clinical Epidemiology and Applied Biostatistics, University of Tübingen, Tübingen, Germany.
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- Jedd D. Wolchok
- 4Memorial Sloan Kettering Cancer Center, New York, New York.
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- Christian Blank
- 3The Netherlands Cancer Institute, Amsterdam, the Netherlands.
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- Graham Pawelec
- 2Department of Internal Medicine II, University Medical Center, Tübingen, Germany.
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- Claus Garbe
- 1Department of Dermatology, University Medical Center, Tübingen, Germany.
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- Benjamin Weide
- 1Department of Dermatology, University Medical Center, Tübingen, Germany.
Description
<jats:title>Abstract</jats:title> <jats:p>Purpose: To identify baseline peripheral blood biomarkers associated with clinical outcome following ipilimumab treatment in advanced melanoma patients.</jats:p> <jats:p>Experimental Design: Frequencies of myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg), serum lactate dehydrogenase (LDH), routine blood counts, and clinical characteristics were assessed in 209 patients. Endpoints were overall survival (OS) and best overall response. Statistical calculations were done by Kaplan–Meier and Cox regression analysis, including calibration and discrimination by C-statistics.</jats:p> <jats:p>Results: Low baseline LDH, absolute monocyte counts (AMC), Lin−CD14+HLA-DR−/low-MDSC frequencies, and high absolute eosinophil counts (AEC), relative lymphocyte counts (RLC), and CD4+CD25+FoxP3+-Treg frequencies were significantly associated with better survival, and were considered in a combination model. Patients (43.5%) presenting with the best biomarker signature had a 30% response rate and median survival of 16 months. In contrast, patients with the worst biomarkers (27.5%) had only a 3% response rate and median survival of 4 months. The occurrence of adverse events correlated with neither baseline biomarker signatures nor the clinical benefit of ipilimumab. In another model, limited to the routine parameters LDH, AMC, AEC, and RLC, the number of favorable factors (4 vs. 3 vs. 2–0) was also associated with OS (P < 0.001 for all pairwise comparisons) in the main study and additionally in an independent validation cohort.</jats:p> <jats:p>Conclusions: A baseline signature of low LDH, AMC, and MDSCs as well as high AEC, Tregs, and RLC is associated with favorable outcome following ipilimumab. Prospective investigation of the predictive impact of these markers following ipilimumab and other treatments, e.g., PD-1 antibodies, is warranted. Clin Cancer Res; 22(12); 2908–18. ©2016 AACR.</jats:p>
Journal
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- Clinical Cancer Research
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Clinical Cancer Research 22 (12), 2908-2918, 2016-06-14
American Association for Cancer Research (AACR)
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Details 詳細情報について
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- CRID
- 1361137044019475712
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- ISSN
- 15573265
- 10780432
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- Data Source
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- Crossref