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Clin Cancer Res. 2016 Jun 15;22(12):2908-18. doi: 10.1158/1078-0432.CCR-15-2412. Epub 2016 Jan 19.

Baseline Peripheral Blood Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated with Ipilimumab.

Author information

1
Department of Dermatology, University Medical Center, Tübingen, Germany. Department of Internal Medicine II, University Medical Center, Tübingen, Germany.
2
The Netherlands Cancer Institute, Amsterdam, the Netherlands.
3
Memorial Sloan Kettering Cancer Center, New York, New York.
4
Memorial Sloan Kettering Cancer Center, New York, New York. Weill Cornell Medical College, New York, New York.
5
Department of Oncology, Service of Medical Oncology, Research Unit 932, Institut Curie, Paris, France.
6
Department of Oncodermatology, INSERM Research Unit 892, University Hospital, Nantes, France.
7
Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy.
8
Division of Medical Oncology and Immunotherapy, University Hospital of Siena, Italy.
9
Department of Dermatology, University Hospital, West German Cancer Center, University Duisburg-Essen, Essen, Germany. German Cancer Consortium (DKTK), Heidelberg, Germany.
10
German Cancer Consortium (DKTK), Heidelberg, Germany. Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
11
Department of Dermatology, University Medical Center, Tübingen, Germany.
12
Departments of Clinical Epidemiology and Applied Biostatistics, University of Tübingen, Tübingen, Germany.
13
Department of Internal Medicine II, University Medical Center, Tübingen, Germany.
14
Department of Dermatology, University Medical Center, Tübingen, Germany. Department of Immunology, University of Tübingen, Tübingen, Germany. benjamin.weide@med.uni-tuebingen.de.

Abstract

PURPOSE:

To identify baseline peripheral blood biomarkers associated with clinical outcome following ipilimumab treatment in advanced melanoma patients.

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.

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.

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.

PMID:
26787752
PMCID:
PMC5770142
DOI:
10.1158/1078-0432.CCR-15-2412
[Indexed for MEDLINE]
Free PMC Article

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