A serum protein signature associated with outcome after anti-PD-1 therapy in metastatic melanoma

Jeffrey S. Weber, Mario Sznol, Ryan J. Sullivan, Shauna Blackmon, Genevieve Boland, Harriet M. Kluger, Ruth Halaban, Antonietta Bacchiocchi, Paolo A. Ascierto, Mariaelena Capone, Carlos Oliveira, Krista Meyer, Julia Grigorieva, Senait G. Asmellash, Joanna Roder, Heinrich Roder

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)79-86
Number of pages8
JournalCancer immunology research
Volume6
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

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ASJC Scopus subject areas

  • Immunology
  • Cancer Research

Cite this

Weber, J. S., Sznol, M., Sullivan, R. J., Blackmon, S., Boland, G., Kluger, H. M., Halaban, R., Bacchiocchi, A., Ascierto, P. A., Capone, M., Oliveira, C., Meyer, K., Grigorieva, J., Asmellash, S. G., Roder, J., & Roder, H. (2018). A serum protein signature associated with outcome after anti-PD-1 therapy in metastatic melanoma. Cancer immunology research, 6(1), 79-86. https://doi.org/10.1158/2326-6066.CIR-17-0412