Clinical Activity of Nivolumab for Human Papilloma Virus-Related Juvenile-Onset Recurrent Respiratory Papillomatosis.

MedStar author(s):
Citation: Oncologist. 24(6):829-835, 2019 06.PMID: 30842242Institution: MedStar Washington Hospital CenterDepartment: OtolaryngologyForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Antineoplastic Agents, Immunological/tu [Therapeutic Use] | *Nivolumab/tu [Therapeutic Use] | *Papillomavirus Infections/th [Therapy] | *Respiratory Tract Infections/th [Therapy] | Adult | Antineoplastic Agents, Immunological/pd [Pharmacology] | Bronchi/dg [Diagnostic Imaging] | Bronchi/pa [Pathology] | Bronchi/su [Surgery] | Bronchi/vi [Virology] | Bronchoscopy | Chemotherapy, Adjuvant/mt [Methods] | Cytoreduction Surgical Procedures | Debridement | Female | Humans | Laryngoscopy | Male | Nivolumab/pd [Pharmacology] | Papillomaviridae/im [Immunology] | Papillomaviridae/ip [Isolation & Purification] | Papillomavirus Infections/im [Immunology] | Papillomavirus Infections/pa [Pathology] | Papillomavirus Infections/vi [Virology] | Programmed Cell Death 1 Receptor/ai [Antagonists & Inhibitors] | Programmed Cell Death 1 Receptor/im [Immunology] | Respiratory Tract Infections/im [Immunology] | Respiratory Tract Infections/pa [Pathology] | Respiratory Tract Infections/vi [Virology] | Tomography, X-Ray Computed | Trachea/dg [Diagnostic Imaging] | Trachea/pa [Pathology] | Trachea/su [Surgery] | Trachea/vi [Virology] | Treatment OutcomeYear: 2019Local holdings: Available online from MWHC library: 1996 - presentISSN:
  • 1083-7159
Name of journal: The oncologistAbstract: 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.CONCLUSION: Nivolumab appears to have promising activity in JO-RRP, and further clinical investigation with more patients in clinical trials is warranted.Copyright (c) AlphaMed Press 2019.IMPLICATIONS FOR PRACTICE: To the authors' knowledge, this article is the first report describing clinical activity with a programed cell death-1 (PD-1) inhibitor to treat a rare but detrimental type of respiratory tract epithelial neoplasm that afflicts young adults. Two patients were treated, and tumor features, such as mutational load, were examined with the intent to stimulate future hypotheses for translational research. The safety and activity of PD-1 inhibitors in this population still need to be corroborated in clinical trials and should not yet be adopted into clinical practice.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.All authors: Ahmad MU, Creelan BC, Grant NN, Kaszuba FJ, Khalil FK, Ozdemirli M, Subramaniam DS, Welsh AWOriginally published: Oncologist. 24(6):829-835, 2019 Jun.Fiscal year: FY2019Digital Object Identifier: Date added to catalog: 2019-08-23
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Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article 30842242 Available 30842242

Available online from MWHC library: 1996 - present

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.

CONCLUSION: Nivolumab appears to have promising activity in JO-RRP, and further clinical investigation with more patients in clinical trials is warranted.

Copyright (c) AlphaMed Press 2019.

IMPLICATIONS FOR PRACTICE: To the authors' knowledge, this article is the first report describing clinical activity with a programed cell death-1 (PD-1) inhibitor to treat a rare but detrimental type of respiratory tract epithelial neoplasm that afflicts young adults. Two patients were treated, and tumor features, such as mutational load, were examined with the intent to stimulate future hypotheses for translational research. The safety and activity of PD-1 inhibitors in this population still need to be corroborated in clinical trials and should not yet be adopted into clinical practice.

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.

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