title: Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab.
abstract: OBJECTIVE
  Biomarkers for outcome after immune-checkpoint blockade are strongly needed as these may influence individual treatment selection or sequence. We aimed to identify baseline factors associated with overall survival (OS) after pembrolizumab treatment in melanoma patients.
  
  
  METHODS
  Serum lactate dehydrogenase (LDH), routine blood count parameters, and clinical characteristics were investigated in 616 patients. Endpoints were OS and best overall response following pembrolizumab treatment. Kaplan-Meier analysis and Cox regression were applied for survival analysis.
  
  
  RESULTS
  Relative eosinophil count (REC) ≥1.5%, relative lymphocyte count (RLC) ≥17.5%, ≤2.5-fold elevation of LDH, and the absence of metastasis other than soft-tissue/lung were associated with favorable OS in the discovery (n = 177) and the confirmation (n = 182) cohort and had independent positive impact (all P < 0.001). Their independent role was subsequently confirmed in the validation cohort (n = 257; all P < 0.01). The number of favorable factors was strongly associated with prognosis. One-year OS probabilities of 83.9% versus 14.7% and response rates of 58.3% versus 3.3% were observed in patients with four of four compared to those with none of four favorable baseline factors present, respectively.
  
  
  CONCLUSIONS
  High REC and RLC, low LDH, and absence of metastasis other than soft-tissue/lung are independent baseline characteristics associated with favorable OS of patients with melanoma treated with pembrolizumab. Presence of four favorable factors in combination identifies a subgroup with excellent prognosis. In contrast, patients with no favorable factors present have a poor prognosis, despite pembrolizumab, and additional treatment advances are still needed. A potential predictive impact needs to be further investigated. Clin Cancer Res; 22(22); 5487-96. ©2016 AACR.
authors.affiliation: Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany. benjamin.weide@med.uni-tuebingen.de.|Department of Immunology, University of Tübingen, Tübingen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Weide
authors.affiliation: Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Martens
authors.affiliation: Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Hassel
authors.affiliation: German Cancer Consortium (DKTK), Heidelberg, Germany.|Department of Dermatology, University Hospital of Munich, Munich, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Berking
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: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Kees
authors.initials: K
authors.lastname: Bisschop
authors.affiliation: Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy.
authors.forename: Ester
authors.initials: E
authors.lastname: Simeone
authors.affiliation: Department of Dermatology, University of Zürich, Zürich, Switzerland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Mangana
authors.affiliation: German Cancer Consortium (DKTK), Heidelberg, Germany.|Department of Dermatology, University Hospital, West German Cancer Center, University Duisburg-Essen, Essen, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Schilling
authors.affiliation: Division of Medical Oncology and Immunotherapy, University Hospital of Siena, Siena, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Di Giacomo
authors.affiliation: Department of Dermatology and Venereology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Brenner
authors.affiliation: Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Kähler
authors.affiliation: Department of Dermatology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Lucie
authors.initials: L
authors.lastname: Heinzerling
authors.affiliation: Skin Cancer Center, Department of Dermatology, Hannover Medical School, Hannover, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gutzmer
authors.affiliation: Department of Dermatology and Allergology, University Hospital of Marburg, Marburg, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Bender
authors.affiliation: German Cancer Consortium (DKTK), Heidelberg, Germany.|Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Department of Dermatology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Gebhardt
authors.affiliation: Department of Oncology, Service of Medical Oncology, Institut Curie, Paris, France.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Romano
authors.affiliation: German Cancer Consortium (DKTK), Heidelberg, Germany.|Department of Dermatology, University Medical Center Dresden, Dresden, Germany.
authors.forename: Friedegund
authors.initials: F
authors.lastname: Meier
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: Division of Medical Oncology and Immunotherapy, University Hospital of Siena, Siena, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Maio
authors.affiliation: Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Christian
authors.initials: C
authors.lastname: Blank
authors.affiliation: German Cancer Consortium (DKTK), Heidelberg, Germany.|Department of Dermatology, University Hospital, West German Cancer Center, University Duisburg-Essen, Essen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.affiliation: Department of Dermatology, University of Zürich, Zürich, Switzerland.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.affiliation: Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy.
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Ascierto
authors.affiliation: Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Geke
authors.initials: G
authors.lastname: Hospers
authors.affiliation: Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
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
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; C582435:pembrolizumab; D007770:L-Lactate Dehydrogenase