TY - JOUR
T1 - A serum protein signature associated with outcome after anti-PD-1 therapy in metastatic melanoma
AU - Weber, Jeffrey S.
AU - Sznol, Mario
AU - Sullivan, Ryan J.
AU - Blackmon, Shauna
AU - Boland, Genevieve
AU - Kluger, Harriet M.
AU - Halaban, Ruth
AU - Bacchiocchi, Antonietta
AU - Ascierto, Paolo A.
AU - Capone, Mariaelena
AU - Oliveira, Carlos
AU - Meyer, Krista
AU - Grigorieva, Julia
AU - Asmellash, Senait G.
AU - Roder, Joanna
AU - Roder, Heinrich
PY - 2018/1/1
Y1 - 2018/1/1
N2 - A mass spectrometry analysis was performed using serum from patients receiving checkpoint inhibitors to define baseline protein signatures associated with outcome in metastatic melanoma. Pretreatment serum was obtained from a development set of 119 melanoma patients on a trial of nivolumab with or without a multipeptide vaccine and from patients receiving pembrolizumab, nivolumab, ipilimumab, or both nivolumab and ipilimumab. Spectra were obtained using matrix-assisted laser desorption/ionization time of flight mass spectrometry. These data combined with clinical data identified patients with better or worse outcomes. The test was applied to five independent patient cohorts treated with checkpoint inhibitors and its biology investigated using enrichment analyses. A signature consisting of 209 proteins or peptides was associated with progression-free and overall survival in a multivariate analysis. The test performance across validation cohorts was consistent with the development set results. A pooled analysis, stratified by set, demonstrated a significantly better overall survival for "sensitive" relative to "resistant" patients, HR = 0.15 (95% confidence interval: 0.06-0.40, P < 0.001). The test was also associated with survival in a cohort of ipilimumab-treated patients. Test classification was found to be associated with acute phase reactant, complement, and wound healing pathways. We conclude that a pretreatment signature of proteins, defined by mass spectrometry analysis and machine learning, predicted survival in patients receiving PD-1 blocking antibodies. This signature of proteins was associated with acute phase reactants and elements of wound healing and the complement cascade. This signature merits further study to determine if it identifies patients who would benefit from PD-1 blockade.
AB - A mass spectrometry analysis was performed using serum from patients receiving checkpoint inhibitors to define baseline protein signatures associated with outcome in metastatic melanoma. Pretreatment serum was obtained from a development set of 119 melanoma patients on a trial of nivolumab with or without a multipeptide vaccine and from patients receiving pembrolizumab, nivolumab, ipilimumab, or both nivolumab and ipilimumab. Spectra were obtained using matrix-assisted laser desorption/ionization time of flight mass spectrometry. These data combined with clinical data identified patients with better or worse outcomes. The test was applied to five independent patient cohorts treated with checkpoint inhibitors and its biology investigated using enrichment analyses. A signature consisting of 209 proteins or peptides was associated with progression-free and overall survival in a multivariate analysis. The test performance across validation cohorts was consistent with the development set results. A pooled analysis, stratified by set, demonstrated a significantly better overall survival for "sensitive" relative to "resistant" patients, HR = 0.15 (95% confidence interval: 0.06-0.40, P < 0.001). The test was also associated with survival in a cohort of ipilimumab-treated patients. Test classification was found to be associated with acute phase reactant, complement, and wound healing pathways. We conclude that a pretreatment signature of proteins, defined by mass spectrometry analysis and machine learning, predicted survival in patients receiving PD-1 blocking antibodies. This signature of proteins was associated with acute phase reactants and elements of wound healing and the complement cascade. This signature merits further study to determine if it identifies patients who would benefit from PD-1 blockade.
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U2 - 10.1158/2326-6066.CIR-17-0412
DO - 10.1158/2326-6066.CIR-17-0412
M3 - Article
AN - SCOPUS:85040461258
VL - 6
SP - 79
EP - 86
JO - Cancer immunology research
JF - Cancer immunology research
SN - 2326-6066
IS - 1
ER -