PD-L1 阻断在侵袭性复发性呼吸道乳头瘤病患者中的安全性和临床活性。
Safety and clinical activity of PD-L1 blockade in patients with aggressive recurrent respiratory papillomatosis.
机构信息
Translational Tumor Immunology Program, National Institute of Deafness and Other Communication Disorders, National Institutes of Health, 10 Center Drive, Room 7N240C, Bethesda, MD, 20892, USA.
Developmental Therapeutics Branch, National Cancer Institute, National Institutes of Health, Bethesda, USA.
出版信息
J Immunother Cancer. 2019 May 3;7(1):119. doi: 10.1186/s40425-019-0603-3.
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.
背景
复发性呼吸道乳头瘤病（RRP）是一种由人乳头瘤病毒（HPV）驱动的疾病，会导致严重的发病率，并可能导致致命的远端气道阻塞和后阻塞性肺炎。患者需要频繁进行手术清创以治疗疾病，但目前尚无批准的系统辅助治疗方法。
方法
进行了一项 II 期研究，以研究程序性死亡配体 1（PD-L1）阻断剂avelumab 在 RRP 患者中的临床活性和安全性。
结果
12 名患者接受了治疗。所有患有喉 RRP 的患者的疾病负担均有所改善，9 名患者中有 5 名（56%）显示部分缓解。4 名患有肺 RRP 的患者均未显示出任何反应。使用每位患者的手术史作为自身对照，avelumab 治疗后患者需要进行的手术干预更少（p=0.008）。一部分部分缓解者的乳头状瘤浸润 T 细胞中出现 HPV 特异性反应，与 HPV 病毒载量降低和组织炎症特征增加相关。
结论
avelumab 在患有喉 RRP 的患者中显示出安全性和临床活性。进一步研究免疫检查点阻断 RRP 的作用，可能需要延长治疗时间或与其他旨在激活抗病毒免疫的免疫疗法联合使用，是有必要的。
试验注册
NCT，编号 NCT02859454，于 2016 年 8 月 9 日注册。
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