TY - JOUR
T1 - Safety and clinical activity of PD-L1 blockade in patients with aggressive recurrent respiratory papillomatosis
AU - Allen, Clint T.
AU - Lee, Sunmin
AU - Norberg, Scott M.
AU - Kovalovsky, Damian
AU - Ye, Hong
AU - Clavijo, Paul E.
AU - Hu-Lieskovan, Siwen
AU - Schlegel, Richard
AU - Schlom, Jeffrey
AU - Strauss, Julius
AU - Gulley, James L.
AU - Trepel, Jane
AU - Hinrichs, Christian S.
N1 - Funding Information:
This work was supported by the Center for Cancer Research, National Cancer Institute, National Institute on Deafness and Other Communication Disorders and the Intramural Research Program of the National Institutes of Health.
Publisher Copyright:
© 2019 The Author(s).
PY - 2019/5/3
Y1 - 2019/5/3
N2 - 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.
AB - 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.
KW - Avelumab
KW - Human papillomavirus
KW - Immune checkpoint inhibition
KW - Recurrent respiratory papillomatosis
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U2 - 10.1186/s40425-019-0603-3
DO - 10.1186/s40425-019-0603-3
M3 - Article
C2 - 31053174
AN - SCOPUS:85065232670
SN - 2051-1426
VL - 7
JO - Journal for immunotherapy of cancer
JF - Journal for immunotherapy of cancer
IS - 1
M1 - 119
ER -