Clinical Activity of Nivolumab for Human Papilloma Virus‐Related Juvenile‐Onset Recurrent Respiratory Papillomatosis. (6th March 2019)

• Record Type: Journal Article
• Authors: Creelan, Ben C.; Ahmad, M. Usman; Kaszuba, Frank J.; Khalil, Farah K.; Welsh, Allison W.; Ozdemirli, Metin; Grant, Nazaneen N.; Subramaniam, Deepa S.
• Is Part Of: Oncologist. Volume 24:Number 6(2019)
• Page Start: 829
• Page End: 835
• Publication Date: 2019-03-06
• Subjects: Recurrent respiratory papillomatosis -- Nivolumab -- Debulking surgical procedures -- Debridement -- Benign neoplasms -- Tracheal stenosis -- Tumor‐infiltrating lymphocytes; Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2018-0505
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract: Background: Juvenile‐onset recurrent respiratory papillomatosis (JO‐RRP) is a human papilloma virus‐mediated progressive benign neoplasm that affects children and young adults. Primary management consists of regular surgical debulking to maintain airway patency and vocal function. Like condyloma acuminata, JO‐RRP is associated with immune dysregulation, and T cells isolated from papillomas express an anergic phenotype. Therefore, we hypothesized that programmed death protein 1 axis inhibition could stabilize tumor growth. Materials and Methods: We treated two patients with refractory JO‐RRP using nivolumab, with the primary objective of assessing clinical activity. We explored baseline papilloma features using immunohistochemistry and comprehensive genomic profiling. Results: Both patients experienced symptomatic improvement, and interval laryngoscopies revealed a reduction in papillomatosis burden. One patient has not required subsequent surgical debridement for almost 2 years. On pathologic examination of pretreatment papillomas from both cases, infiltrating T cells were evident in the papilloma stroma, and papilloma programmed death ligand 1 expression was absent. Papilloma mutational load ranged between three and six mutations per megabase for each case. From on‐treatment biopsy tissue, a higher amount of intraepithelial T cells and programmed death ligand 1 expression were detected in the papilloma. Conclusion: Nivolumab appears to have promising activity in JO‐RRP, and further clinical investigation with more patients in clinical trials is warranted. Abstract : Juvenile onset recurrent respiratory papillomatosis (JO‐RRP) is a benign neoplasm of the larynx that affects children and young adults. This article assesses the clinical activity of nivolumab treatment in two patients with JO‐RRP.