Immune-related thyroid dysfunctions during anti PD-1/PD-L1 inhibitors: new evidence from a single centre experience.
Anti-thyroid peroxidase antibodies
Hypothyroidism
Immune checkpoint inhibitors
Survival
Thyrotoxicosis
Journal
Clinical and experimental medicine
ISSN: 1591-9528
Titre abrégé: Clin Exp Med
Pays: Italy
ID NLM: 100973405
Informations de publication
Date de publication:
27 Apr 2023
27 Apr 2023
Historique:
received:
01
04
2023
accepted:
20
04
2023
medline:
27
4
2023
pubmed:
27
4
2023
entrez:
27
4
2023
Statut:
aheadofprint
Résumé
The role of anti-thyroid peroxidase antibodies (anti-TPO Abs) in the development of abnormal thyroid function tests (DYSTHYR) during treatment with immune checkpoint inhibitors (ICIs) is not fully understood; moreover, controversial data exist about the relationship between ICI-related thyroid dysfunction (TD) and survival. We retrospectively analyzed the onset or the worsening of DYSTHYR in patients treated with programmed cell death protein-1 (PD-1) or its ligand (PD-L1) inhibitors between 2017 and 2020. In patients without previous TD, we focused on the association between baseline anti-TPO Abs level and DYSTHYR. Furthermore, the relationship between DYSTHYR and progression-free survival (PFS) or overall survival (OS) was explored. We included 324 patients treated with anti PD-1 (95.4%) or anti PD-L1 inhibitors. After a median of 3.3 months, DYSTHYR was registered in 24.7%, mostly hypothyroidism alone (17%). Patients with pre-existing TD (14.5% of the sample) were at higher risk of DYSTHYR compared to patients without previous TD (adjusted OR 2.44; 95% IC 1.26-4.74). In patients without known previous TD, high anti-TPO Abs level, even below the positivity cut-off, was a risk factor for developing DYSTHYR (adjusted OR 5.52; 95% IC 1.47-20.74). DYSTHYR was associated with a longer 12-month OS (87.3% vs 73.5%, p = 0.03); no statistically significant difference in terms of PFS was observed between the DYSTHYR+ and DYSTHYR- group. DYSTHYR is common during anti PD-1/anti PD-L1 treatment, especially in patients with pre-existing TD. In subjects without known previous TD, high anti-TPO Abs level at baseline can be a predictive biomarker of DYSTHYR. An improved OS is observed in patients with anti PD-1/anti PD-L1-induced DYSTHYR.
Identifiants
pubmed: 37103651
doi: 10.1007/s10238-023-01082-5
pii: 10.1007/s10238-023-01082-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Références
Elia G, Ferrari SM, Galdiero MR, et al. New insight in endocrine-related adverse events associated to immune checkpoint blockade. Best Pract Res Clin Endocrinol Metab. 2020;34:101370. https://doi.org/10.1016/j.beem.2019.101370 .
doi: 10.1016/j.beem.2019.101370
pubmed: 31983543
Muir CA, Tsang VHM, Menzies AM, Clifton-Bligh RJ. Immune related adverse events of the thyroid—a narrative review. Front Endocrinol (Lausanne). 2022;13:886930. https://doi.org/10.3389/fendo.2022.886930 .
doi: 10.3389/fendo.2022.886930
pubmed: 35692394
Barroso-Sousa R, Ott PA, Hodi FS, et al. Endocrine dysfunction induced by immune checkpoint inhibitors: practical recommendations for diagnosis and clinical management. Cancer. 2018;124:1111–21. https://doi.org/10.1002/cncr.31200 .
doi: 10.1002/cncr.31200
pubmed: 29313945
Yoon JH, Hong AR, Kim HK, Kang H-C. Characteristics of immune-related thyroid adverse events in patients treated with PD-1/PD-L1 inhibitors. Endocrinol Metab (Seoul). 2021;36:413–23. https://doi.org/10.3803/EnM.2020.906 .
doi: 10.3803/EnM.2020.906
pubmed: 33820396
Iwama S, Kobayashi T, Yasuda Y, Arima H. Immune checkpoint inhibitor-related thyroid dysfunction. Best Pract Res Clin Endocrinol Metab. 2022;36:101660. https://doi.org/10.1016/j.beem.2022.101660 .
doi: 10.1016/j.beem.2022.101660
pubmed: 35501263
Okada N, Iwama S, Okuji T, et al. Anti-thyroid antibodies and thyroid echo pattern at baseline as risk factors for thyroid dysfunction induced by anti-programmed cell death-1 antibodies: a prospective study. Br J Cancer. 2020;122:771–7. https://doi.org/10.1038/s41416-020-0736-7 .
doi: 10.1038/s41416-020-0736-7
pubmed: 32009131
pmcid: 7078193
Lee H, Hodi FS, Giobbie-Hurder A, et al. Characterization of thyroid disorders in patients receiving immune checkpoint inhibition therapy. Cancer Immunol Res. 2017;5:1133–40. https://doi.org/10.1158/2326-6066.CIR-17-0208 .
doi: 10.1158/2326-6066.CIR-17-0208
pubmed: 29079654
pmcid: 5748517
Mosaferi T, Tsai K, Sovich S, et al. Optimal thyroid hormone replacement dose in immune checkpoint inhibitor-associated hypothyroidism is distinct from Hashimoto’s thyroiditis. Thyroid. 2022;32:496–504. https://doi.org/10.1089/thy.2021.0685 .
doi: 10.1089/thy.2021.0685
pubmed: 35199588
Brilli L, Danielli R, Campanile M, et al. Baseline serum TSH levels predict the absence of thyroid dysfunction in cancer patients treated with immunotherapy. J Endocrinol Invest. 2021;44:1719–26. https://doi.org/10.1007/s40618-020-01480-6 .
doi: 10.1007/s40618-020-01480-6
pubmed: 33367977
Cheung Y-MM, Wang W, McGregor B, Hamnvik O-PR. Associations between immune-related thyroid dysfunction and efficacy of immune checkpoint inhibitors: a systematic review and meta-analysis. Cancer Immunol Immunother. 2022;71:1795–812. https://doi.org/10.1007/s00262-021-03128-7 .
doi: 10.1007/s00262-021-03128-7
pubmed: 35022907
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47. https://doi.org/10.1016/j.ejca.2008.10.026 .
doi: 10.1016/j.ejca.2008.10.026
pubmed: 19097774
Campredon P, Mouly C, Lusque A, et al. Incidence of thyroid dysfunctions during treatment with nivolumab for non-small cell lung cancer: Retrospective study of 105 patients. Presse Med. 2019;48:e199–207. https://doi.org/10.1016/j.lpm.2018.10.019 .
doi: 10.1016/j.lpm.2018.10.019
pubmed: 31005502
Peiró I, Palmero R, Iglesias P, et al. Thyroid dysfunction induced by nivolumab: searching for disease patterns and outcomes. Endocrine. 2019;64:605–13. https://doi.org/10.1007/s12020-019-01871-7 .
doi: 10.1007/s12020-019-01871-7
pubmed: 30805887
Castinetti F, Albarel F, Archambeaud F, et al. French endocrine society guidance on endocrine side effects of immunotherapy. Endocr Relat Cancer. 2019;26:G1–18. https://doi.org/10.1530/ERC-18-0320 .
doi: 10.1530/ERC-18-0320
pubmed: 30400055
Husebye ES, Castinetti F, Criseno S, et al. Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline. Eur J Endocrinol. 2022;187:G1–21. https://doi.org/10.1530/EJE-22-0689 .
doi: 10.1530/EJE-22-0689
pubmed: 36149449
pmcid: 9641795
Patrizio A, Fallahi P, Antonelli A, Ferrari SM. Immune checkpoint inhibitor-induced thyroid disorders: a single center experience. Curr Pharm Des. 2023;29:295–9. https://doi.org/10.2174/1381612828666220518151509 .
doi: 10.2174/1381612828666220518151509
pubmed: 35593347
Pollack RM, Kagan M, Lotem M, Dresner-Pollak R. Baseline TSH level is associated with risk of ANTI-PD-1-induced thyroid dysfunction. Endocr Pract. 2019;25:824–9. https://doi.org/10.4158/EP-2018-0472 .
doi: 10.4158/EP-2018-0472
pubmed: 31013164
Kimbara S, Fujiwara Y, Iwama S, et al. Association of antithyroglobulin antibodies with the development of thyroid dysfunction induced by nivolumab. Cancer Sci. 2018;109:3583–90. https://doi.org/10.1111/cas.13800 .
doi: 10.1111/cas.13800
pubmed: 30230649
pmcid: 6215874
Izawa N, Shiokawa H, Onuki R, et al. The clinical utility of comprehensive measurement of autoimmune disease-related antibodies in patients with advanced solid tumors receiving immune checkpoint inhibitors: a retrospective study. ESMO Open. 2022;7:100415. https://doi.org/10.1016/j.esmoop.2022.100415 .
doi: 10.1016/j.esmoop.2022.100415
pubmed: 35247869
pmcid: 9058890
Kotwal A, Kottschade L, Ryder M. PD-L1 inhibitor-induced thyroiditis is associated with better overall survival in cancer patients. Thyroid. 2020;30:177–84. https://doi.org/10.1089/thy.2019.0250 .
doi: 10.1089/thy.2019.0250
pubmed: 31813343
pmcid: 7047075
Muir CA, Wood CCG, Clifton-Bligh RJ, et al. Association of antithyroid antibodies in checkpoint inhibitor-associated thyroid immune-related adverse events. J Clin Endocrinol Metab. 2022;107:e1843–9. https://doi.org/10.1210/clinem/dgac059 .
doi: 10.1210/clinem/dgac059
pubmed: 35104870
Lima Ferreira J, Costa C, Marques B, et al. Improved survival in patients with thyroid function test abnormalities secondary to immune-checkpoint inhibitors. Cancer Immunol Immunother. 2021;70:299–309. https://doi.org/10.1007/s00262-020-02664-y .
doi: 10.1007/s00262-020-02664-y
pubmed: 32712715
Kotwal A, Ryder M. Survival benefit of endocrine dysfunction following immune checkpoint inhibitors for nonthyroidal cancers. Curr Opin Endocrinol Diabetes Obes. 2021;28:517–24. https://doi.org/10.1097/MED.0000000000000664 .
doi: 10.1097/MED.0000000000000664
pubmed: 34269714
Frelau A, Jali E, Campillo-Gimenez B, et al. Prognostic impact of thyroid dysfunctions on progression-free survival in patients with metastatic melanoma treated with anti-PD-1 antibodies. Melanoma Res. 2021;31:208–17. https://doi.org/10.1097/CMR.0000000000000739 .
doi: 10.1097/CMR.0000000000000739
pubmed: 33904517
Yirgin IK, Erturk SM, Dogan I, Vatansever S. Are radiologists ready to evaluate true response to immunotherapy? Insights Imaging. 2021;12:29. https://doi.org/10.1186/s13244-021-00968-w .
doi: 10.1186/s13244-021-00968-w
pubmed: 33625595
pmcid: 7905005
Seymour L, Bogaerts J, Perrone A, et al. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 2017;18:e143–52. https://doi.org/10.1016/S1470-2045(17)30074-8 .
doi: 10.1016/S1470-2045(17)30074-8
pubmed: 28271869
pmcid: 5648544