title: Baseline Peripheral Blood Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated with Ipilimumab.
abstract: To identify baseline peripheral blood biomarkers associated with clinical outcome following ipilimumab treatment in advanced melanoma patients.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Dermatology, University Medical Center, Tübingen, Germany. Department of Internal Medicine II, University Medical Center, Tübingen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Martens
authors.affiliation: Department of Dermatology, University Medical Center, Tübingen, Germany. Department of Internal Medicine II, University Medical Center, Tübingen, Germany.
authors.forename: Kilian
authors.initials: K
authors.lastname: Wistuba-Hamprecht
authors.affiliation: The Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Marnix
authors.initials: M
authors.lastname: Geukes Foppen
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Jianda
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York. Weill Cornell Medical College, New York, New York.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Postow
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Phillip
authors.initials: P
authors.lastname: Wong
authors.affiliation: Department of Oncology, Service of Medical Oncology, Research Unit 932, Institut Curie, Paris, France.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Romano
authors.affiliation: Department of Oncodermatology, INSERM Research Unit 892, University Hospital, Nantes, France.
authors.forename: Amir
authors.initials: A
authors.lastname: Khammari
authors.affiliation: Department of Oncodermatology, INSERM Research Unit 892, University Hospital, Nantes, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dreno
authors.affiliation: Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy.
authors.forename: Mariaelena
authors.initials: M
authors.lastname: Capone
authors.affiliation: Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy.
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Ascierto
authors.affiliation: Division of Medical Oncology and Immunotherapy, University Hospital of Siena, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Di Giacomo
authors.affiliation: Division of Medical Oncology and Immunotherapy, University Hospital of Siena, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
authors.affiliation: Department of Dermatology, University Hospital, West German Cancer Center, University Duisburg-Essen, Essen, Germany. German Cancer Consortium (DKTK), Heidelberg, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Schilling
authors.affiliation: Department of Dermatology, University Hospital, West German Cancer Center, University Duisburg-Essen, Essen, Germany. German Cancer Consortium (DKTK), Heidelberg, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Sucker
authors.affiliation: Department of Dermatology, University Hospital, West German Cancer Center, University Duisburg-Essen, Essen, Germany. German Cancer Consortium (DKTK), Heidelberg, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.affiliation: German Cancer Consortium (DKTK), Heidelberg, Germany. Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Hassel
authors.affiliation: Department of Dermatology, University Medical Center, Tübingen, Germany.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Eigentler
authors.affiliation: Departments of Clinical Epidemiology and Applied Biostatistics, University of Tübingen, Tübingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Martus
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York. Weill Cornell Medical College, New York, New York.
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
authors.affiliation: The Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Christian
authors.initials: C
authors.lastname: Blank
authors.affiliation: Department of Internal Medicine II, University Medical Center, Tübingen, Germany.
authors.forename: Graham
authors.initials: G
authors.lastname: Pawelec
authors.affiliation: Department of Dermatology, University Medical Center, Tübingen, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
authors.affiliation: Department of Dermatology, University Medical Center, Tübingen, Germany. Department of Immunology, University of Tübingen, Tübingen, Germany. benjamin.weide@med.uni-tuebingen.de.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Weide
mesh_terms: D000368:Aged; D000074322:Antineoplastic Agents, Immunological / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D004906:Erythrocyte Count; D005260:Female; D006801:Humans; D000074324:Ipilimumab / Q000009:adverse effects / Q000627:therapeutic use*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D018655:Lymphocyte Count; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000072737:Myeloid-Derived Suppressor Cells / Q000166:cytology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology; D016896:Treatment Outcome
chemical_list: D000074322:Antineoplastic Agents, Immunological; D014408:Biomarkers, Tumor; D000074324:Ipilimumab; D007770:L-Lactate Dehydrogenase