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      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Durable and dramatic response to checkpoint inhibition combined with COX‐2 inhibitor celecoxib in a patient with p16+ metastatic sinonasal undifferentiated carcinoma: A case study

      case-report

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          Abstract

          Background

          Sinonasal undifferentiated carcinoma (SNUC) is an exceedingly rare head and neck malignancy. No consensus exists on treatment for metastatic disease.

          Case

          A 56‐year‐old female was diagnosed with SNUC after endorsing sinus congestion, diplopia, and right orbital pain. Initially treated with surgery and radiation, she later developed significant metastatic disease. She demonstrated progression of her hepatic metastases under pembrolizumab therapy. However, the addition of ipilimumab and a COX‐2 inhibitor resulted in significant improvement in her lesions as well as an ongoing durable response. Her regimen was complicated by immune‐related adverse events successfully treated with steroids.

          Conclusion

          Dual checkpoint inhibition deserves consideration when treating metastatic SNUC, especially after single agent therapy has failed. The positive effect of this treatment may be augmented by IDO1 inhibition.

          Related collections

          Most cited references12

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          Head and neck squamous cell carcinoma

          Daniel E. Johnson, Barbara Burtness, C. René Leemans … (2020)
          Most head and neck cancers are derived from the mucosal epithelium in the oral cavity, pharynx and larynx and are known collectively as head and neck squamous cell carcinoma (HNSCC). Oral cavity and larynx cancers are generally associated with tobacco consumption, alcohol abuse or both, whereas pharynx cancers are increasingly attributed to infection with human papillomavirus (HPV), primarily HPV-16. Thus, HNSCC can be separated into HPV-negative or HPV-positive HNSCC. Despite evidence of histological progression from cellular atypia through various degrees of dysplasia, ultimately leading to invasive HNSCC, most patients are diagnosed with late-stage HNSCC without a clinically evident antecedent premalignant lesion. Traditional staging of HNSCC using the tumour-node-metastasis system has been supplemented by the 2017 AJCC/UICC staging system, which incorporated additional information relevant to HPV-positive disease. The treatment approach is generally multimodal, consisting of surgery followed by chemotherapy plus radiation (chemoradiation or CRT) for oral cavity cancers and primary CRT for pharynx and larynx cancers. The EGFR monoclonal antibody cetuximab is generally used in combination with radiation in HPV-negative HNSCC where co-morbidities prevent the use of cytotoxic chemotherapy. The FDA approved the immune checkpoint inhibitors pembrolizumab and nivolumab for treatment of recurrent or metastatic HNSCC and pembrolizumab as primary treatment for unresectable disease. Elucidation of the molecular genetic landscape of HNSCC over the past decade has revealed new opportunities for therapeutic intervention. Ongoing efforts aim to integrate our understanding of HNSCC biology and immunobiology to identify predictive biomarkers that will enable delivery of the most effective, least toxic therapies.
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            Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors

            Satya Ranjan Das, Douglas Johnson (2019)
            Although immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for patients with many advanced malignancies, only 15–60% of patients respond, leaving a broad swath of patients who do not derive benefit. Identifying biomarkers to optimally identify patients who will benefit from ICIs is a major research focus for the oncology community. Thus far, predictive biomarker research has focused on tumor signatures such as microsatellite instability, programmed death-ligand 1 (PD-L1) expression and tumor mutational burden; clinical biomarkers have been far less studied. One potential clinical biomarker for ICI response in patients is immune-related adverse event (IRAE) onset. IRAEs are thought to represent bystander effects from activated T-cells and it is plausible that patients responding to ICIs would have greater likelihood of autoimmune toxicities (e.g. due to a more competent/treatment-responsive immune system, or cross-reactivity between tumor and host tissue). Earlier studies in melanoma patients however, suggested no association between IRAE onset and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody efficacy. In contrast, a growing body of literature suggests IRAE onset is predictive of anti-programmed cell death protein 1 (PD-1) and anti-PD-L1 antibody response across a variety of solid tumors. Most of these studies report that patients who experienced IRAEs demonstrate marked improvements in progression-free survival, overall survival and overall response rate compared to those lacking toxicity. Key questions regarding the association between IRAE onset and ICI efficacy remain. The most pertinent of these involve whether the association is only relevant for patients treated with anti-PD-1 and anti-PD-L1 antibodies and whether IRAE site, severity, timing of onset and management influence ICI efficacy. Herein, we discuss the seminal studies which have begun to address these questions and have shaped the narrative about the predictive value of IRAE onset for patients on ICIs, in this review.
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              Prevalence of PDL1 Amplification and Preliminary Response to Immune Checkpoint Blockade in Solid Tumors

              Aaron M Goodman, David Piccioni, Shumei Kato … (2018)
              Copy number alterations in programmed cell death ligand 1 (PDL1 or CD274), programmed cell death 1 ligand 2 (PDCD1LG2 or PDL2), and Janus kinase 2 (JAK2) genes (chromosome 9p24.1) characterize Hodgkin lymphoma, resulting in high response rates to programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) blockade. The prevalence and utility of PDL1 amplification as a response biomarker to PD-1/PD-L1 blockade are unknown in other tumors.
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                Author and article information

                Contributors
                Jonathan Q. Trinh:
                ORCID: https://orcid.org/0000-0001-7830-1792
                jtrinh@unmc.edu
                Journal
                Journal ID (nlm-ta): Cancer Rep (Hoboken)
                Journal ID (iso-abbrev): Cancer Rep (Hoboken)
                Journal ID (doi): 10.1002/(ISSN)2573-8348
                Journal ID (publisher-id): CNR2
                Title: Cancer Reports
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Electronic): 2573-8348
                Publication date (Electronic): 22 October 2023
                Publication date Collection: January 2024
                Volume: 7
                Issue: 1 ( doiID: 10.1002/cnr2.v7.1 )
                Electronic Location Identifier: e1915
                Affiliations
                [ 1 ] Department of Internal Medicine University of Nebraska Medical Center Omaha Nebraska USA
                [ 2 ] Department of Medical Oncology and Hematology City of Hope Goodyear Arizona USA
                [ 3 ] Department of Pathology and Laboratory Medicine City of Hope Goodyear Arizona USA
                [ 4 ] Department of Internal Medicine Rush University Medical Center Chicago Illinois USA
                Author notes
                [*] [* ] Correspondence

                Jonathan Q. Trinh, Department of Internal Medicine, University of Nebraska Medical Center, 982055 Nebraska Medical Center, Omaha, NE 68198‐2055, USA.

                Email: jtrinh@ 123456unmc.edu

                Author information
                https://orcid.org/0000-0001-7830-1792
                Article
                Publisher ID: CNR21915
                DOI: 10.1002/cnr2.1915
                PMC ID: 10809189
                PubMed ID: 37867289
                SO-VID: b01a135f-6e4d-48cf-adfa-6778162d3641
                Copyright © © 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date revision received : 01 October 2023
                Date received : 22 May 2023
                Date accepted : 08 October 2023
                Page count
                Figures: 2, Tables: 2, Pages: 5, Words: 2831
                Categories
                Subject: Case Report
                Subject: Case Report
                Custom metadata
                source-schema-version-number 2.0
                cover-date January 2024
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.6 mode:remove_FC converted:25.01.2024

                Keywords: dual checkpoint inhibition,ido1,immunotherapy,metastatic,sinonasal undifferentiated carcinoma
                Data availability:
                Keywords: dual checkpoint inhibition, ido1, immunotherapy, metastatic, sinonasal undifferentiated carcinoma

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