Baseline biomarkers for outcome of melanoma patients treated with pembrolizumab
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 Desig...
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| Hauptverfasser: | , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
May 16, 2016
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| In: |
Clinical cancer research
Year: 2016, Jahrgang: 22, Heft: 22, Pages: 5487-5496 |
| ISSN: | 1557-3265 |
| DOI: | 10.1158/1078-0432.CCR-16-0127 |
| Online-Zugang: | Verlag, Volltext: https://doi.org/10.1158/1078-0432.CCR-16-0127 Verlag, Volltext: http://clincancerres.aacrjournals.org/content/22/22/5487 
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| Verfasserangaben: | 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 Kähler, 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, and Jedd D. Wolchok |
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| 245 | 1 | 0 | |a Baseline biomarkers for outcome of melanoma patients treated with pembrolizumab |c 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 Kähler, 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, and Jedd D. Wolchok |
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| 520 | |a 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. | ||
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