Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages
| Autor: | Jacob Mandel, Padmanee Sharma, Ganesh Rao, Shouhao Zhou, Jorge Blando, Be Lian Pei, Jimin Wu, Kathy Hunter, Monica Loghin, Shalini S. Yadav, Gregory N. Fuller, Sujit S. Prabhu, Ying Yuan, Frederick F. Lang, Rivka R. Colen, Raymond Sawaya, W. K. Alfred Yung, Carlos Kamiya Matsouka, Jeffrey S. Weinberg, Jason T. Huse, Amy B. Heimberger, James P. Allison, Kristin Alfaro-Munoz, Sherise D. Ferguson, John de Groot, Ian E. McCutcheon, Barbara O’Brien, Luis M Vence, Marta Penas-Prado, Shiao Pei Weathers |
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| Rok vydání: | 2019 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Clinical Investigations Pembrolizumab Antibodies Monoclonal Humanized Immune system Stable Disease Internal medicine Tumor Microenvironment medicine Humans Macrophage Tumor microenvironment CD68 business.industry Macrophages Editorials medicine.disease Progression-Free Survival Immunity Innate Clinical trial Neurology (clinical) Glioblastoma business Progressive disease |
| Zdroj: | Neuro Oncol |
| ISSN: | 1523-5866 1522-8517 |
| Popis: | Background We sought to ascertain the immune effector function of pembrolizumab within the glioblastoma (GBM) microenvironment during the therapeutic window. Methods 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. Results 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. Conclusions 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. |
| Databáze: | OpenAIRE |
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