Baseline biomarkers for outcome of melanoma patients treated with pembrolizumab Journal Article


Authors: 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.; Kähler, K.; Heinzerling, L.; Gutzmer, R.; Bender, A.; Gebhardt, C.; Romano, E.; Meier, F.; Martus, P.; Maio, M.; Blank, C.; Schadendorf, D.; Dummer, R.; Ascierto, P. A.; Hospers, G.; Garbe, C.; Wolchok, J. D.
Article Title: Baseline biomarkers for outcome of melanoma patients treated with pembrolizumab
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. (C)2016 AACR.
Keywords: ipilimumab; melanoma; safety; metastatic melanoma; cell lung-cancer; t-cells; responses; untreated; nivolumab; lactate-dehydrogenase; pd-1 blockade
Journal Title: Clinical Cancer Research
Volume: 22
Issue: 22
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2016-11-01
Start Page: 5487
End Page: 5496
Language: English
ACCESSION: WOS:000388743600014
DOI: 10.1158/1078-0432.ccr-16-0127
PROVIDER: wos
PUBMED: 27185375
PMCID: PMC5572569
Notes: Article -- Source: Wos
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MSK Authors
  1. Jedd D Wolchok
    629 Wolchok
  2. Michael Andrew Postow
    180 Postow