Association of antithyroglobulin antibodies with the development of thyroid dysfunction induced by nivolumab
Open accessAbstract
Thyroid dysfunction (TD) induced by immune checkpoint inhibitors is not sufficiently understood. The purpose of this retrospective observational study was to identify risk factors and the clinical course of TD induced by nivolumab. Patients with advanced solid tumors who were treated with nivolumab from March 2009 through to March 2016 at the National Cancer Center Hospital (Tokyo, Japan) were included. Thyroid function and antithyroid Abs from serum samples among all patients were evaluated at baseline and during nivolumab treatment. Overt hypothyroidism was defined as low serum-free T4 together with elevated thyroid-stimulating hormone (TSH) >10 μIU/mL. Thyrotoxicosis was defined as low TSH with elevated free T4 and/or free T3. We defined thyroid autoimmunity as the presence of antithyroid Abs at baseline, including antithyroid peroxidase Abs and antithyroglobulin Abs (TgAb). Twenty-three (14%) of a total of 168 patients developed TD, including 17 cases of hypothyroidism and 20 of thyrotoxicosis. Thyrotoxicosis followed by hypothyroidism occurred in 14 cases. Fourteen of 35 patients (40%) with thyroid autoimmunity developed TD vs 9 of 133 (7%) without (odds ratio 9.19; 95% confidence interval [CI], 3.53-23.9). In multivariate analysis, elevated TSH and TgAb at baseline were significantly associated with the development of TD, with odds ratio of 7.36 (95% CI, 1.66-32.7) and 26.5 (95% CI, 8.18-85.8), respectively. Association between TD and elevated antithyroid peroxidase Abs at baseline was not significant. These results suggest that patients with pre-existing TgAb and elevated TSH at baseline are at high risk of TD.
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Positive TPOAb and/or thyroglobulin autoantibodies (TgAb) are associated with a 40 to 70% risk of hypothyroidism during immune checkpoint inhibitor (ICPi) treatment.
“Two retrospective and two prospective studies reported that positive TPOAb and/or thyroglobulin autoantibodies (TgAb) are associated with a 40 to 70% risk of hypothyroidism during treatment”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [57]
The Results section (page not available) reports thyroid dysfunction in 40% of patients with baseline thyroid autoimmunity and 63% of those with TgAb during nivolumab treatment. Those figures are for thyroid dysfunction, which includes thyrotoxicosis, rather than specifically hypothyroidism. TPOAb alone was not significantly associated with thyroid dysfunction; 2 of 16 patients with TPOAb alone developed it. (LLM, conf=0.90)
Experimental — accuracy not yet measuredCorticosteroid therapy may influence the course of ICPi-induced thyroid dysfunction.
“Corticosteroid therapy may influence the course of ICPi-induced thyroid dysfunction [57,61].”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [57]
Patients who had ICPi-induced hypothyroidism had positive anti-thyroid autoantibodies in 75 to 100% of cases.
“and that patients who had ICPi-induced hypothyroidism had positive anti-thyroid autoantibodies in 75 to 100% of cases [54,55,56,57].”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [57]
In Kimbara et al., of 20 patients with induced thyrotoxicosis, five of the six who did not develop secondary hypothyroidism had received corticosteroid therapy for another reason.
“Kimbara et al. noted that of 20 patients with induced thyrotoxicosis, five of the six who did not develop secondary hypothyroidism had received corticosteroid therapy for another reason [57].”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [57]
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Cites
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155 · see citing works
Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer
Reck, M., Rodríguez-Abreu, D., Robinson, A. G., Hui, R., Csőszi, T., Fülöp, A., Gottfried, M., Peled, N., Tafreshi, A., Cuffe, S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1606774 · Cited by 10,089 · see citing works
Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D. R., Steins, M., Ready, N. E., Chow, L. Q., Vokes, E. E., Felip, E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1507643 · Cited by 9,335 · see citing works
Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer
Brahmer, J., Reckamp, K. L., Baas, P., Crinò, L., Eberhardt, W. E. E., Poddubskaya, E., Antonia, S., Pluzanski, A., Vokes, E. E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504627 · Cited by 8,447 · see citing works
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma
Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J. J., Cowey, C. L., Lao, C. D., Schadendorf, D., Dummer, R., Smylie, M., Rutkowski, P., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504030 · Cited by 8,157 · see citing works
Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer
Garon, E. B., Rizvi, N. A., Hui, R., Leighl, N., Balmanoukian, A. S., Eder, J. P., Patnaik, A., Aggarwal, C., Gubens, M., Horn, L., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1501824 · Cited by 6,198 · see citing works
Pembrolizumab versus Ipilimumab in Advanced Melanoma
Robert, C., Schachter, J., Long, G. V., Arance, A., Grob, J. J., Mortier, L., Daud, A., Carlino, M. S., McNeil, C., Lotem, M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1503093 · Cited by 5,887 · see citing works
Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma
Motzer, R. J., Escudier, B., McDermott, D. F., George, S., Hammers, H. J., Srinivas, S., Tykodi, S. S., Sosman, J. A., Procopio, G., Plimack, E. R., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1510665 · Cited by 5,807 · see citing works
Nivolumab in Previously Untreated Melanoma without <i>BRAF</i> Mutation
Robert, C., Long, G. V., Brady, B., Dutriaux, C., Maio, M., Mortier, L., Hassel, J. C., Rutkowski, P., McNeil, C., Kalinka-Warzocha, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1412082 · Cited by 5,519 · see citing works
Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck
Ferris, R. L., Blumenschein, G., Fayette, J., Guigay, J., Colevas, A. D., Licitra, L., Harrington, K., Kasper, S., Vokes, E. E., Even, C., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1602252 · Cited by 5,101 · see citing works
Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma
Robert, C., Thomas, L., Bondarenko, I., O'Day, S., Weber, J., Garbe, C., Lebbe, C., Baurain, J.-F., Testori, A., Grob, J.-J., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1104621 · Cited by 4,496 · see citing works
Brahmer, J. R., Lacchetti, C., Schneider, B. J., Atkins, M. B., Brassil, K. J., Caterino, J. M., Chau, I., Ernstoff, M. S., Gardner, J. M., Ginex, P., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.77.6385 · Cited by 3,713 · see citing works
Rosenberg, J. E., Hoffman-Censits, J., Powles, T., van der Heijden, M. S., Balar, A. V., Necchi, A., Dawson, N., O'Donnell, P. H., Balmanoukian, A., Loriot, Y., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00561-4 · Cited by 3,669 · see citing works
Weber, J. S., D’Angelo, S. P., Minor, D. R., Hodi, F. S., Gutzmer, R., Neyns, B., Höeller, C., Khushalani, N. I., Miller, W. H., Lao, C. D., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)70076-8 · Cited by 2,676 · see citing works
Association of Immune-Related Adverse Events With Nivolumab Efficacy in Non–Small-Cell Lung Cancer
Haratani, K., Hayashi, H., Chiba, Y., Kudo, K., Yonesaka, K., Kato, R., Kaneda, H., Hasegawa, Y., Tanaka, K., Takeda, M., et al. (2018) · JAMA Oncology · doi:10.1001/jamaoncol.2017.2925 · Cited by 1,003 · see citing works
Chen, R., Zinzani, P. L., Fanale, M. A., Armand, P. A., Johnson, N. A., Brice, P., Radford, J. A., Ribrag, V., Molin, D. L., Vassilakopoulos, T. P., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.72.1316 · Cited by 991 · see citing works
Younes, A., Santoro, A., Shipp, M. A., Zinzani, P. L., Timmerman, J. M., Ansell, S. M., Armand, P. A., Fanale, M. A., Ratanatharathorn, V., Kuruvilla, J. G., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30167-x · Cited by 928 · see citing works
Freeman-Keller, M., Kim, Y., Cronin, H., Richards, A., Gibney, G., & Weber, J. S. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1136 · Cited by 863 · see citing works
Sharma, P., Callahan, M. K., Bono, P., Kim, J. W., Spiliopoulou, P., Calvo, E., Pillai, R. N., Ott, P. A., de Braud, F., Morse, M. A., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30496-x · Cited by 676 · see citing works
Osorio, J. C., Ni, A., Chaft, J. E., Pollina, R., Kasler, M. K., Stephens, D., Rodriguez, C., Cambridge, L., Rizvi, H., Wolchok, J. D., et al. (2017) · Annals of Oncology · doi:10.1093/annonc/mdw640 · Cited by 659 · see citing works
Downey, S. G., Klapper, J. A., Smith, F. O., Yang, J. C., Sherry, R. M., Royal, R. E., Kammula, U. S., Hughes, M. S., Allen, T. E., Levy, C. L., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0187 · Cited by 624 · see citing works
Endocrine Side Effects Induced by Immune Checkpoint Inhibitors
Corsello, S. M., Barnabei, A., Marchetti, P., De Vecchis, L., Salvatori, R., & Torino, F. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-4075 · Cited by 403 · see citing works
Brahmer, J. R., Lacchetti, C., & Thompson, J. A. (2018) · Journal of Oncology Practice · doi:10.1200/jop.18.00005 · Cited by 377 · see citing works
Kobayashi, T., Iwama, S., Yasuda, Y., Okada, N., Tsunekawa, T., Onoue, T., Takagi, H., Hagiwara, D., Ito, Y., Morishita, Y., et al. (2018) · Journal of the Endocrine Society · doi:10.1210/js.2017-00432 · Cited by 203 · see citing works
Self-citationEndocrine side effects of cancer immunotherapy
Cukier, P., Santini, F. C., Scaranti, M., & Hoff, A. O. (2017) · Endocrine-Related Cancer · doi:10.1530/erc-17-0358 · Cited by 177 · see citing works
Nakamura, Y., Kitano, S., Takahashi, A., Tsutsumida, A., Namikawa, K., Tanese, K., Abe, T., Funakoshi, T., Yamamoto, N., Amagai, M., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.12677 · Cited by 166 · see citing works
Self-citationOrlov, S., Salari, F., Kashat, L., & Walfish, P. G. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-4560 · Cited by 134 · see citing works
Ali, O. H., Diem, S., Markert, E., Jochum, W., Kerl, K., French, L. E., Speiser, D. E., Früh, M., & Flatz, L. (2016) · OncoImmunology · doi:10.1080/2162402x.2016.1231292 · Cited by 116 · see citing works
Kanda, S., Goto, K., Shiraishi, H., Kubo, E., Tanaka, A., Utsumi, H., Sunami, K., Kitazono, S., Mizugaki, H., Horinouchi, H., et al. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw416 · Cited by 94 · see citing works
Self-citationPhase I study of Nivolumab, an anti-PD-1 antibody, in patients with malignant solid tumors
Yamamoto, N., Nokihara, H., Yamada, Y., Shibata, T., Tamura, Y., Seki, Y., Honda, K., Tanabe, Y., Wakui, H., & Tamura, T. (2016) · Investigational New Drugs · doi:10.1007/s10637-016-0411-2 · Cited by 91 · see citing works
Self-citationEhlers, M., Thiel, A., Bernecker, C., Porwol, D., Papewalis, C., Willenberg, H. S., Schinner, S., Hautzel, H., Scherbaum, W. A., & Schott, M. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2178 · Cited by 79 · see citing works
Yamazaki, N., Kiyohara, Y., Uhara, H., Uehara, J., Fujimoto, M., Takenouchi, T., Otsuka, M., Uchi, H., Ihn, H., & Minami, H. (2017) · Cancer Science · doi:10.1111/cas.13241 · Cited by 71 · see citing works
Self-citationNishio, M., Hida, T., Atagi, S., Sakai, H., Nakagawa, K., Takahashi, T., Nogami, N., Saka, H., Takenoyama, M., Maemondo, M., et al. (2017) · ESMO Open · doi:10.1136/esmoopen-2016-000108 · Cited by 69 · see citing works
Self-citationHida, T., Nishio, M., Nogami, N., Ohe, Y., Nokihara, H., Sakai, H., Satouchi, M., Nakagawa, K., Takenoyama, M., Isobe, H., et al. (2017) · Cancer Science · doi:10.1111/cas.13225 · Cited by 62 · see citing works
Self-citationKiyohara, Y., Uhara, H., Ito, Y., Matsumoto, N., Tsuchida, T., & Yamazaki, N. (2018) · The Journal of Dermatology · doi:10.1111/1346-8138.14227 · Cited by 51 · see citing works
Self-citationHodi, F. S., Postow, M. A., Chesney, J. A., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.15_suppl.9518 · Cited by 20 · see citing works
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Okada, N., Iwama, S., Okuji, T., Kobayashi, T., Yasuda, Y., Wada, E., Onoue, T., Goto, M., Sugiyama, M., Tsunekawa, T., et al. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-0736-7 · Cited by 78 · see citing works
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“noted that of 20 patients with induced thyrotoxicosis, five of the six who did not develop secondary hypothyroidism had received corticosteroid therapy for another reason [57].”
Background
- Authors
- Kimbara, S., Fujiwara, Y., Iwama, S., Ohashi, K., Kuchiba, A., Arima, H., Yamazaki, N., Kitano, S., Yamamoto, N., & Ohe, Y.
- Affiliations
- Kobe University Hospital (JP)
- National Cancer Center Hospital (JP)
- Nagoya University (JP)
- National Cancer Centre Japan (JP)
- Corresponding author
- Fujiwara, Yutaka
- ORCID
- Venue
- Cancer Science
- Publisher
- Wiley
- Published
- 2018-10-13
- Volume
- 109
- Issue
- 11
- Pages
- 3583-3590
- ISSN
- 1347-9032 (ISSN-L)
- 1349-7006
- PMC
- PMC6215874
- OpenAlex
- W2889824011
- Cited by
- 158
- References
- 36
- Citations by year
- 2026: 5 · 2025: 23 · 2024: 15 · 2023: 28 · 2022: 24 · 2021: 26 · 2020: 24 · 2019: 12 · 2018: 1
- FWCI
- 12.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancer Science (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- Bristol-Myers Squibb
- Ono Pharmaceutical
- Japan Society for the Promotion of Science (16K19552)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- thyroid dysfunction, nivolumab, immune checkpoint inhibitors, thyroglobulin antibodies, thyroid peroxidase antibodies, hypothyroidism, thyrotoxicosis, thyroid autoimmunity, thyroid-stimulating hormone, risk factors, advanced solid tumors
- MeSH terms
- Nivolumab, Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Autoantibodies, Female, Humans, Hypothyroidism, Japan, Male, Middle Aged, Retrospective Studies, Thyroid Diseases, Thyroid Gland, Thyrotoxicosis, Thyrotropin, Odds Ratio, Young Adult
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