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Clin Cancer Res. 2016 Nov 15;22(22):5487-5496. doi: 10.1158/1078-0432.CCR-16-0127. Epub 2016 May 16.

Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab.

Author information

1
Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany. benjamin.weide@med.uni-tuebingen.de.
2
Department of Immunology, University of Tübingen, Tübingen, Germany.
3
Department of Dermatology, University Medical Center Tübingen, Tübingen, Germany.
4
Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.
5
German Cancer Consortium (DKTK), Heidelberg, Germany.
6
Department of Dermatology, University Hospital of Munich, Munich, Germany.
7
Memorial Sloan Kettering Cancer Center, New York, New York.
8
Weill Cornell Medical College, New York, New York.
9
Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
10
Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy.
11
Department of Dermatology, University of Zürich, Zürich, Switzerland.
12
Department of Dermatology, University Hospital, West German Cancer Center, University Duisburg-Essen, Essen, Germany.
13
Division of Medical Oncology and Immunotherapy, University Hospital of Siena, Siena, Italy.
14
Department of Dermatology and Venereology, University Hospital of Cologne, Cologne, Germany.
15
Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany.
16
Department of Dermatology, University Hospital Erlangen, Erlangen, Germany.
17
Skin Cancer Center, Department of Dermatology, Hannover Medical School, Hannover, Germany.
18
Department of Dermatology and Allergology, University Hospital of Marburg, Marburg, Germany.
19
Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
20
Department of Dermatology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.
21
Department of Oncology, Service of Medical Oncology, Institut Curie, Paris, France.
22
Department of Dermatology, University Medical Center Dresden, Dresden, Germany.
23
Departments of Clinical Epidemiology and Applied Biostatistics, University of Tübingen, Tübingen, Germany.
24
Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.

Abstract

PURPOSE:

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.

EXPERIMENTAL DESIGN:

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.

PMID:
27185375
PMCID:
PMC5572569
DOI:
10.1158/1078-0432.CCR-16-0127
[Indexed for MEDLINE]
Free PMC Article

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