Durvalumab-induced Thyroiditis in a Patient with Non-small Cell Lung Carcinoma: a Case Report and Review of Pathogenic Mechanisms

Overview

Journal BMC Endocr Disord

Publisher Biomed Central

Specialty Endocrinology

Date 2022 Nov 24

PMID 36419114

Authors

Jeroen M K de Filette

Stephanie Andre

Lynn De Mey

Sandrine Aspeslagh

Rafik Karmali

Bart J Van der Auwera

Bert Bravenboer

Affiliations

Soon will be listed here.

Abstract

Background: Immune checkpoint inhibitors (ICI) targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 and its ligand (PD-1/PD-L1) have become the current standard-of-care for advanced cancers. This novel therapeutic approach comes with its costs in the form of immune-related adverse events (irAE), including endocrinopathy.

Case Presentation: A 63-year-old woman was diagnosed with a non-small cell lung carcinoma of the right superior lobe, cT3N2M0. She developed thyrotoxicosis followed by hypothyroidism induced by consolidation immunotherapy with durvalumab (anti-PD-L1). Analysis of the human leukocyte antigen (HLA) region showed HLA-DR4 (susceptible) and DR13 (protective). The possible mechanisms are subsequently discussed in detail.

Conclusions: The case of a patient with thyroiditis associated with the PD-L1 inhibitor durvalumab is described, highlighting the need for proactive monitoring of thyroid hormone levels. Identifying biomarkers associated with an increased risk of ICI-induced side effects (such as HLA) is of interest for better patient selection, optimal management and improved understanding of the mechanisms involved.

Citing Articles

Toxicity in the era of immune checkpoint inhibitor therapy.

Keam S, Turner N, Kugeratski F, Rico R, Colunga-Minutti J, Poojary R Front Immunol. 2024; 15:1447021.

PMID: 39247203 PMC: 11377343. DOI: 10.3389/fimmu.2024.1447021.

Endocrine side effects of immune checkpoint inhibitors.

Cardona Z, Sosman J, Chandra S, Huang W Front Endocrinol (Lausanne). 2023; 14:1157805.

PMID: 37251665 PMC: 10210589. DOI: 10.3389/fendo.2023.1157805.

References

Heward J, Allahabadia A, Daykin J, Carr-Smith J, Daly A, Armitage M . Linkage disequilibrium between the human leukocyte antigen class II region of the major histocompatibility complex and Graves' disease: replication using a population case control and family-based study. J Clin Endocrinol Metab. 1998; 83(10):3394-7. DOI: 10.1210/jcem.83.10.5137. View

Brancatella A, Viola N, Brogioni S, Montanelli L, Sardella C, Vitti P . Graves' Disease Induced by Immune Checkpoint Inhibitors: A Case Report and Review of the Literature. Eur Thyroid J. 2019; 8(4):192-195. PMC: 6738242. DOI: 10.1159/000501824. View

de Filette J, Pen J, Decoster L, Vissers T, Bravenboer B, Van der Auwera B . Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review. Eur J Endocrinol. 2019; 181(3):363-374. PMC: 6709545. DOI: 10.1530/EJE-19-0291. View

Zaborowski M, Sywak M, Nylen C, Gill A, Chou A . Unique and distinctive histological features of immunotherapy-related thyroiditis. Pathology. 2020; 52(2):271-273. DOI: 10.1016/j.pathol.2019.10.010. View

Delivanis D, Gustafson M, Bornschlegl S, Merten M, Kottschade L, Withers S . Pembrolizumab-Induced Thyroiditis: Comprehensive Clinical Review and Insights Into Underlying Involved Mechanisms. J Clin Endocrinol Metab. 2017; 102(8):2770-2780. PMC: 5546861. DOI: 10.1210/jc.2017-00448. View

Angell T, Min L, Wieczorek T, Hodi F . Unique Cytologic Features of Thyroiditis Caused by Immune Checkpoint Inhibitor Therapy for Malignant Melanoma. Genes Dis. 2018; 5(1):46-48. PMC: 5879785. DOI: 10.1016/j.gendis.2017.11.002. View

Correale P, Saladino R, Nardone V, Giannicola R, Agostino R, Pirtoli L . Could PD-1/PDL1 immune checkpoints be linked to HLA signature?. Immunotherapy. 2019; 11(18):1523-1526. DOI: 10.2217/imt-2019-0160. View

Mekki A, Dercle L, Lichtenstein P, Marabelle A, Michot J, Lambotte O . Detection of immune-related adverse events by medical imaging in patients treated with anti-programmed cell death 1. Eur J Cancer. 2018; 96:91-104. DOI: 10.1016/j.ejca.2018.03.006. View

Min L, Vaidya A, Becker C . Thyroid autoimmunity and ophthalmopathy related to melanoma biological therapy. Eur J Endocrinol. 2010; 164(2):303-7. PMC: 4080629. DOI: 10.1530/EJE-10-0833. View

10.

Kurihara S, Oikawa Y, Nakajima R, Satomura A, Tanaka R, Kagamu H . Simultaneous development of Graves' disease and type 1 diabetes during anti-programmed cell death-1 therapy: A case report. J Diabetes Investig. 2020; 11(4):1006-1009. PMC: 7378416. DOI: 10.1111/jdi.13212. View

11.

Kobayashi T, Iwama S, Yasuda Y, Okada N, Tsunekawa T, Onoue T . Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study. J Endocr Soc. 2018; 2(3):241-251. PMC: 5836529. DOI: 10.1210/js.2017-00432. View

12.

Yajima K, Akise Y . A Case Report of Graves' Disease Induced by the Anti-Human Programmed Cell Death-1 Monoclonal Antibody Pembrolizumab in a Bladder Cancer Patient. Case Rep Endocrinol. 2019; 2019:2314032. PMC: 6854234. DOI: 10.1155/2019/2314032. View

13.

Simmonds M, Howson J, Heward J, Cordell H, Foxall H, Carr-Smith J . Regression mapping of association between the human leukocyte antigen region and Graves disease. Am J Hum Genet. 2004; 76(1):157-63. PMC: 1196419. DOI: 10.1086/426947. View

14.

Cappelli L, Dorak M, Bettinotti M, Bingham C, Shah A . Association of HLA-DRB1 shared epitope alleles and immune checkpoint inhibitor-induced inflammatory arthritis. Rheumatology (Oxford). 2018; 58(3):476-480. PMC: 6821338. DOI: 10.1093/rheumatology/key358. View

15.

Imblum B, Baloch Z, Fraker D, LiVolsi V . Pembrolizumab-Induced Thyroiditis. Endocr Pathol. 2019; 30(2):163-167. DOI: 10.1007/s12022-019-9579-2. View

16.

Damsky W, Jilaveanu L, Turner N, Perry C, Zito C, Tomayko M . B cell depletion or absence does not impede anti-tumor activity of PD-1 inhibitors. J Immunother Cancer. 2019; 7(1):153. PMC: 6567557. DOI: 10.1186/s40425-019-0613-1. View

17.

Iadarola C, Croce L, Quaquarini E, Teragni C, Pinto S, Bernardo A . Nivolumab Induced Thyroid Dysfunction: Unusual Clinical Presentation and Challenging Diagnosis. Front Endocrinol (Lausanne). 2019; 9:813. PMC: 6345097. DOI: 10.3389/fendo.2018.00813. View

18.

Ramos-Levi A, Rogado J, Sanchez-Torres J, Colomer R, Marazuela M . Nivolumab-induced thyroid dysfunction in patients with lung cancer. Endocrinol Diabetes Nutr (Engl Ed). 2018; 66(1):26-34. DOI: 10.1016/j.endinu.2018.05.005. View

19.

McElnea E, Ni Mhealoid A, Moran S, Kelly R, Fulcher T . Thyroid-like ophthalmopathy in a euthyroid patient receiving Ipilimumab. Orbit. 2014; 33(6):424-7. DOI: 10.3109/01676830.2014.949792. View

20.

Sabini E, Sframeli A, Marino M . A case of drug-induced Graves' Orbitopathy after combination therapy with Tremelimumab and Durvalumab. J Endocrinol Invest. 2018; 41(7):877-878. DOI: 10.1007/s40618-018-0906-0. View