Abstract
BackgroundRecurrent 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.MethodsA 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.ResultsTwelve 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.ConclusionsAvelumab 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 registrationNCT, number NCT02859454, registered August 9, 2016.
Highlights
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
Recurrent respiratory papillomatosis (RRP) is a clinical disorder characterized by aerodigestive tract papillomas that cause severe voice disturbance, airway obstruction, and potentially fatal distal small-airway obstruction leading to post-obstructive pneumonias [1, 2]
There was a trend toward greater likelihood of experiencing a partial response to avelumab in patients with RRP associated with HPV 6 compared to HPV 11, this failed to reach statistical significance in this small cohort (Additional file 1: Figure S1)
Summary
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. Recurrent respiratory papillomatosis (RRP) is a clinical disorder characterized by aerodigestive tract papillomas that cause severe voice disturbance, airway obstruction, and potentially fatal distal small-airway obstruction leading to post-obstructive pneumonias [1, 2]. Surgical debridement of papillomas is the standard of care treatment approach, and patients with aggressive RRP can undergo. We report clinical and immune correlative findings from a phase II clinical trial for the treatment of patients with aggressive RRP with avelumab, an FDA-approved anti-PD-L1 monoclonal antibody (mAb) [13, 14]
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