Safety and clinical activity of PD-L1 blockade in patients with aggressive recurrent respiratory papillomatosis

Clint T. Allen, Sunmin Lee, Scott M. Norberg, Damian Kovalovsky, Hong Ye, Paul E. Clavijo, Siwen Hu-Lieskovan, Richard Schlegel, Jeffrey Schlom, Julius Strauss, James L. Gulley, Jane Trepel, Christian S. Hinrichs

Research output: Contribution to journalArticle

Abstract

Background: Recurrent respiratory papillomatosis (RRP) is a human papillomavirus (HPV)-driven disorder that causes substantial morbidity and can lead to fatal distal airway obstruction and post-obstructive pneumonias. Patients require frequent surgical debridement of disease, and no approved systemic adjuvant therapies exist. Methods: A phase II study was conducted to investigate the clinical activity and safety of programmed death-ligand 1 (PD-L1) blockade with avelumab in patients with RRP. Results: Twelve patients were treated. All patients with laryngeal RRP displayed improvement in disease burden, and 5 of 9 (56%) displayed partial responses. None of 4 patients with pulmonary RRP displayed a response. Using each patient's surgical history as their own control, patients required fewer surgical interventions after avelumab treatment (p = 0.008). A subset of partial responders developed HPV-specific reactivity in papilloma-infiltrating T-cells that correlated with reduced HPV viral load and an increased Tissue Inflammation Signature. Conclusions: Avelumab demonstrated safety and clinical activity in patients with laryngeal RRP. Further study of immune checkpoint blockade for RRP, possibly with longer treatment duration or in combination with other immunotherapies aimed at activating antiviral immunity, is warranted. Trial registration: NCT, number NCT02859454, registered August 9, 2016.

Original languageEnglish (US)
Article number119
JournalJournal for immunotherapy of cancer
Volume7
Issue number1
DOIs
StatePublished - May 3 2019

Keywords

  • Avelumab
  • Human papillomavirus
  • Immune checkpoint inhibition
  • Recurrent respiratory papillomatosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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    Allen, C. T., Lee, S., Norberg, S. M., Kovalovsky, D., Ye, H., Clavijo, P. E., Hu-Lieskovan, S., Schlegel, R., Schlom, J., Strauss, J., Gulley, J. L., Trepel, J., & Hinrichs, C. S. (2019). Safety and clinical activity of PD-L1 blockade in patients with aggressive recurrent respiratory papillomatosis. Journal for immunotherapy of cancer, 7(1), [119]. https://doi.org/10.1186/s40425-019-0603-3