Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab

Benjamin Weide; Alexander Martens; Jessica C. Hassel; Carola Berking; Michael A. Postow; Kees Bisschop; Ester Simeone; Johanna Mangana; Bastian Schilling; Anna Maria Di Giacomo; Nicole Brenner; Katharina Kaehler; Lucie Heinzerling; Ralf Gutzmer; Armin Bender; Christoffer Gebhardt; Emanuela Romano; Friedegund Meier; Peter Martus; Michele Maio; Christian Blank; Dirk Schadendorf; Reinhard Dummer; Paolo A. Ascierto; Geke Hospers; Claus Garbe; Jedd D. Wolchok

doi:10.1158/1078-0432.CCR-16-0127

Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab

Benjamin Weide^*, Alexander Martens, Jessica C. Hassel, Carola Berking, Michael A. Postow, Kees Bisschop, Ester Simeone, Johanna Mangana, Bastian Schilling, Anna Maria Di Giacomo, Nicole Brenner, Katharina Kaehler, Lucie Heinzerling, Ralf Gutzmer, Armin Bender, Christoffer Gebhardt, Emanuela Romano, Friedegund Meier, Peter Martus, Michele MaioChristian Blank, Dirk Schadendorf, Reinhard Dummer, Paolo A. Ascierto, Geke Hospers, Claus Garbe, Jedd D. Wolchok

^*Corresponding author for this work

Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Research output: Contribution to journal › Article › Academic › peer-review

279 Citations (Scopus)

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%,

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. (C)2016 AACR.

Original language	English
Pages (from-to)	5487-5496
Number of pages	10
Journal	Clinical Cancer Research
Volume	22
Issue number	22
DOIs	https://doi.org/10.1158/1078-0432.CCR-16-0127
Publication status	Published - 15-Nov-2016

Keywords

CELL LUNG-CANCER
METASTATIC MELANOMA
LACTATE-DEHYDROGENASE
UNTREATED MELANOMA
PD-1 BLOCKADE
T-CELLS
IPILIMUMAB
NIVOLUMAB
SAFETY
RESPONSES

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Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab
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Weide, B., Martens, A., Hassel, J. C., Berking, C., Postow, M. A., Bisschop, K., Simeone, E., Mangana, J., Schilling, B., Di Giacomo, A. M., Brenner, N., Kaehler, K., Heinzerling, L., Gutzmer, R., Bender, A., Gebhardt, C., Romano, E., Meier, F., Martus, P., ... Wolchok, J. D. (2016). Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab. Clinical Cancer Research, 22(22), 5487-5496. https://doi.org/10.1158/1078-0432.CCR-16-0127

Weide, Benjamin ; Martens, Alexander ; Hassel, Jessica C. ; Berking, Carola ; Postow, Michael A. ; Bisschop, Kees ; Simeone, Ester ; Mangana, Johanna ; Schilling, Bastian ; Di Giacomo, Anna Maria ; Brenner, Nicole ; Kaehler, Katharina ; Heinzerling, Lucie ; Gutzmer, Ralf ; Bender, Armin ; Gebhardt, Christoffer ; Romano, Emanuela ; Meier, Friedegund ; Martus, Peter ; Maio, Michele ; Blank, Christian ; Schadendorf, Dirk ; Dummer, Reinhard ; Ascierto, Paolo A. ; Hospers, Geke ; Garbe, Claus ; Wolchok, Jedd D. / Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab. In: Clinical Cancer Research. 2016 ; Vol. 22, No. 22. pp. 5487-5496.

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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%,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. (C)2016 AACR.",

keywords = "CELL LUNG-CANCER, METASTATIC MELANOMA, LACTATE-DEHYDROGENASE, UNTREATED MELANOMA, PD-1 BLOCKADE, T-CELLS, IPILIMUMAB, NIVOLUMAB, SAFETY, RESPONSES",

author = "Benjamin Weide and Alexander Martens and Hassel, {Jessica C.} and Carola Berking and Postow, {Michael A.} and Kees Bisschop and Ester Simeone and Johanna Mangana and Bastian Schilling and {Di Giacomo}, {Anna Maria} and Nicole Brenner and Katharina Kaehler and Lucie Heinzerling and Ralf Gutzmer and Armin Bender and Christoffer Gebhardt and Emanuela Romano and Friedegund Meier and Peter Martus and Michele Maio and Christian Blank and Dirk Schadendorf and Reinhard Dummer and Ascierto, {Paolo A.} and Geke Hospers and Claus Garbe and Wolchok, {Jedd D.}",

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Weide, B, Martens, A, Hassel, JC, Berking, C, Postow, MA, Bisschop, K, Simeone, E, Mangana, J, Schilling, B, Di Giacomo, AM, Brenner, N, Kaehler, K, Heinzerling, L, Gutzmer, R, Bender, A, Gebhardt, C, Romano, E, Meier, F, Martus, P, Maio, M, Blank, C, Schadendorf, D, Dummer, R, Ascierto, PA, Hospers, G, Garbe, C & Wolchok, JD 2016, 'Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab', Clinical Cancer Research, vol. 22, no. 22, pp. 5487-5496. https://doi.org/10.1158/1078-0432.CCR-16-0127

Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab. / Weide, Benjamin; Martens, Alexander; Hassel, Jessica C.; Berking, Carola; Postow, Michael A.; Bisschop, Kees; Simeone, Ester; Mangana, Johanna; Schilling, Bastian; Di Giacomo, Anna Maria; Brenner, Nicole; Kaehler, Katharina; Heinzerling, Lucie; Gutzmer, Ralf; Bender, Armin; Gebhardt, Christoffer; Romano, Emanuela; Meier, Friedegund; Martus, Peter; Maio, Michele; Blank, Christian; Schadendorf, Dirk; Dummer, Reinhard; Ascierto, Paolo A.; Hospers, Geke; Garbe, Claus; Wolchok, Jedd D.

In: Clinical Cancer Research, Vol. 22, No. 22, 15.11.2016, p. 5487-5496.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab

AU - Weide, Benjamin

AU - Martens, Alexander

AU - Hassel, Jessica C.

AU - Berking, Carola

AU - Postow, Michael A.

AU - Bisschop, Kees

AU - Simeone, Ester

AU - Mangana, Johanna

AU - Schilling, Bastian

AU - Di Giacomo, Anna Maria

AU - Brenner, Nicole

AU - Kaehler, Katharina

AU - Heinzerling, Lucie

AU - Gutzmer, Ralf

AU - Bender, Armin

AU - Gebhardt, Christoffer

AU - Romano, Emanuela

AU - Meier, Friedegund

AU - Martus, Peter

AU - Maio, Michele

AU - Blank, Christian

AU - Schadendorf, Dirk

AU - Dummer, Reinhard

AU - Ascierto, Paolo A.

AU - Hospers, Geke

AU - Garbe, Claus

AU - Wolchok, Jedd D.

PY - 2016/11/15

Y1 - 2016/11/15

N2 - 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%,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. (C)2016 AACR.

AB - 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%,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. (C)2016 AACR.

KW - CELL LUNG-CANCER

KW - METASTATIC MELANOMA

KW - LACTATE-DEHYDROGENASE

KW - UNTREATED MELANOMA

KW - PD-1 BLOCKADE

KW - T-CELLS

KW - IPILIMUMAB

KW - NIVOLUMAB

KW - SAFETY

KW - RESPONSES

U2 - 10.1158/1078-0432.CCR-16-0127

DO - 10.1158/1078-0432.CCR-16-0127

M3 - Article

VL - 22

SP - 5487

EP - 5496

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 22

ER -