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de Groot, John; Penas-Prado, Marta; Alfaro-Munoz, Kristin; Hunter, Kathy; Pei, Be Lian; O’Brien, Barbara; Weathers, Shiao-Pei; Loghin, Monica; Kamiya Matsouka, Carlos; Yung, W K Alfred; Mandel, Jacob; Wu, Jimin; Yuan, Ying; Zhou, Shouhao; Fuller, Gregory N; Huse, Jason; Rao, Ganesh; Weinberg, Jeffrey S; Prabhu, Sujit S; McCutcheon, Ian E; Lang, Frederick F; Ferguson, Sherise D; Sawaya, Raymond; Colen, Rivka; [...]

Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages

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  • Medientyp: E-Artikel
  • Titel: Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages
  • Beteiligte: de Groot, John; Penas-Prado, Marta; Alfaro-Munoz, Kristin; Hunter, Kathy; Pei, Be Lian; O’Brien, Barbara; Weathers, Shiao-Pei; Loghin, Monica; Kamiya Matsouka, Carlos; Yung, W K Alfred; Mandel, Jacob; Wu, Jimin; Yuan, Ying; Zhou, Shouhao; Fuller, Gregory N; Huse, Jason; Rao, Ganesh; Weinberg, Jeffrey S; Prabhu, Sujit S; McCutcheon, Ian E; Lang, Frederick F; Ferguson, Sherise D; Sawaya, Raymond; Colen, Rivka; [...]
  • Erschienen: Oxford University Press (OUP), 2020
  • Erschienen in: Neuro-Oncology
  • Sprache: Englisch
  • DOI: 10.1093/neuonc/noz185
  • ISSN: 1522-8517; 1523-5866
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>We sought to ascertain the immune effector function of pembrolizumab within the glioblastoma (GBM) microenvironment during the therapeutic window.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>In an open-label, single-center, single-arm phase II “window-of-opportunity” trial in 15 patients with recurrent (operable) GBM receiving up to 2 pembrolizumab doses before surgery and every 3 weeks afterward until disease progression or unacceptable toxicities occurred, immune responses were evaluated within the tumor.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>No treatment-related deaths occurred. Overall median follow-up time was 50 months. Of 14 patients monitored, 10 had progressive disease, 3 had a partial response, and 1 had stable disease. Median progression-free survival (PFS) was 4.5 months (95% CI: 2.27, 6.83), and the 6-month PFS rate was 40%. Median overall survival (OS) was 20 months, with an estimated 1-year OS rate of 63%. GBM patients’ recurrent tumors contained few T cells that demonstrated a paucity of immune activation markers, but the tumor microenvironment was markedly enriched for CD68+ macrophages.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Immune analyses indicated that pembrolizumab anti–programmed cell death 1 (PD-1) monotherapy alone can’t induce effector immunologic response in most GBM patients, probably owing to a scarcity of T cells within the tumor microenvironment and a CD68+ macrophage preponderance.</jats:p> </jats:sec>
  • Zugangsstatus: Freier Zugang