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Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer
Open accessAbstract
Background Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated durable responses and prolonged survival in a variety of malignancies. Treatment is generally well tolerated although immune-related adverse events (irAEs) can occur. Autoimmune thyroid dysfunction is among the most common irAE, but an assessment of the clinical, mechanistic, and immunologic features has not been previously described.Patient and methods Patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab at Memorial Sloan Kettering Cancer Center (n = 51) as part of KEYNOTE-001 (NCT01295827) were included. Thyroid function test and anti-thyroid antibodies were assessed prospectively at each study visit, beginning before the first treatment. Frequency of development of thyroid dysfunction, association with anti-thyroid antibodies, clinical course, and relationship with progression-free survival and overall survival to treatment with pembrolizumab was evaluated.Results Of 51 patients treated, 3 were hypothyroid and 48 were not at baseline. Ten of 48 [21%, 95% confidence interval (CI) 10% to 35%] patients developed thyroid dysfunction requiring thyroid replacement. Anti-thyroid antibodies were present in 8 of 10 patients who developed thyroid dysfunction, compared with 3 of 38 who did not (80% versus 8%, P < 0.0001). Thyroid dysfunction occurred early (median, 42 days) in the pembrolizumab course, and a majority (6 of 10 patients) experienced brief, transient hyperthyroidism preceding the onset of hypothyroidism; no persistent hyperthyroidism occurred. Both hyperthyroidism and hypothyroidism were largely asymptomatic. Overall survival with pembrolizumab was significantly longer in subjects who developed thyroid dysfunction (hazard ratio, 0.29; 95% CI 0.09-0.94; P = 0.04).Conclusions Thyroid dysfunction during pembrolizumab treatment of NSCLC is common and is characterized by early-onset, frequently preceded by transient hyperthyroidism, closely associated with anti-thyroid antibodies, and may be associated with improved outcomes. The presence of antibody-mediated toxicity in T-cell-directed therapy suggests an under-recognized impact of PD-1 biology in modulating humoral immunity.
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“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 [56]
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“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 [56]
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“Note that in the Osorio study [56], survival was better if patients developed ICPi-induced thyroid dysfunction”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [56]
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Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,320
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
Self-citationHollowell, J. G., Staehling, N. W., Flanders, W. D., Hannon, W. H., Gunter, E. W., Spencer, C. A., & Braverman, L. E. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.87.2.489 · Cited by 4,279
Ishida, Y., Agata, Y., Shibahara, K., & Honjo, T. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05481.x · Cited by 3,259
Nishimura, H., Nose, M., Hiai, H., Minato, N., & Honjo, T. (1999) · Immunity · doi:10.1016/s1074-7613(00)80089-8 · Cited by 2,749
CTLA-4 and PD-1 Receptors Inhibit T-Cell Activation by Distinct Mechanisms
Parry, R. V., Chemnitz, J. M., Frauwirth, K. A., Lanfranco, A. R., Braunstein, I., Kobayashi, S. V., Linsley, P. S., Thompson, C. B., & Riley, J. L. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.21.9543-9553.2005 · Cited by 1,931
Garber, J. R., Cobin, R. H., Gharib, H., Hennessey, J. V., Klein, I., Mechanick, J. I., Pessah-Pollack, R., Singer, P. A., & Woeber, K. A. (2012) · Endocrine Practice · doi:10.4158/ep12280.gl · Cited by 1,567
Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma
Ribas, A., Hamid, O., Daud, A., Hodi, F. S., Wolchok, J. D., Kefford, R., Joshua, A. M., Patnaik, A., Hwu, W.-J., Weber, J. S., et al. (2016) · JAMA · doi:10.1001/jama.2016.4059 · Cited by 1,069
Self-citation2013 ETA Guideline: Management of Subclinical Hypothyroidism
Pearce, S. H. S., Brabant, G., Duntas, L. H., Monzani, F., Peeters, R. P., Razvi, S., & Wemeau, J.-L. (2013) · European Thyroid Journal · doi:10.1159/000356507 · Cited by 877
Cited by
Sorted by citations
Immune-Related Adverse Events Associated with Immune Checkpoint Blockade
Postow, M. A., Sidlow, R., & Hellmann, M. D. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1703481 · Cited by 4,849
Self-citationInflammation and tumor progression: signaling pathways and targeted intervention
Zhao, H., Wu, L., Yan, G., Chen, Y., Zhou, M., Wu, Y., & Li, Y. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00658-5 · Cited by 3,058
Haanen, J. B. A. G., Carbonnel, F., Robert, C., Kerr, K. M., Peters, S., Larkin, J., & Jordan, K. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx225 · Cited by 2,367
“Recently, a cohort of 51 NSCLC patients treated with pembrolizumab in the Keynote-001 study was prospectively followed by thyroid-stimulating hormone (TSH), triiodothyronine and thyroxine (FT3, FT4) and anti-thyroid antibodies (Abs) measurement [28].”
BackgroundA review of cancer immunotherapy toxicity
Kennedy, L. B., & Salama, A. K. S. (2020) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21596 · Cited by 1,396
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
Brahmer, J. R., Abu-Sbeih, H., Ascierto, P. A., Brufsky, J., Cappelli, L. C., Cortazar, F. B., Gerber, D. E., Hamad, L., Hansen, E., Johnson, D. B., et al. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-002435 · Cited by 917
Thompson, J. A., Schneider, B. J., Brahmer, J., Andrews, S., Armand, P., Bhatia, S., Budde, L. E., Costa, L., Davies, M., Dunnington, D., et al. (2019) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2019.0013 · Cited by 570
Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints
Chang, L., Barroso‐Sousa, R., Tolaney, S. M., Hodi, F. S., Kaiser, U. B., & Min, L. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00006 · Cited by 550
Cortellini, A., Bersanelli, M., Buti, S., Cannita, K., Santini, D., Perrone, F., Giusti, R., Tiseo, M., Michiara, M., Di Marino, P., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0527-y · Cited by 413
Immune-checkpoint inhibitors associated with interstitial lung disease in cancer patients
Delaunay, M., Cadranel, J., Lusque, A., Meyer, N., Gounant, V., Moro-Sibilot, D., Michot, J.-M., Raimbourg, J., Girard, N., Guisier, F., et al. (2017) · European Respiratory Journal · doi:10.1183/13993003.00050-2017 · Cited by 412
Early B cell changes predict autoimmunity following combination immune checkpoint blockade
Das, R., Bar, N., Ferreira, M., Newman, A. M., Zhang, L., Bailur, J. K., Bacchiocchi, A., Kluger, H., Wei, W., Halaban, R., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci96798 · Cited by 423
Hussaini, S. M. Q., Chehade, R., Boldt, G., Raphael, J., Blanchette, P., Vareki, S. M., & Fernandes, R. (2020) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2020.102134 · Cited by 412
Teraoka, S., Fujimoto, D., Morimoto, T., Kawachi, H., Ito, M., Sato, Y., Nagata, K., Nakagawa, A., Otsuka, K., Uehara, K., et al. (2017) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2017.08.022 · Cited by 375
“Recently, dermatological irAEs and immunotherapy-related thyroid dysfunction have been associated with a clinical benefit to ICIs in patients with NSCLC.(16,17) However, no prospective clinical trials have been conducted and little is known regarding the association between irAEs and the outcome of patients with NSCLC…”
BackgroundThe Diverse Function of PD-1/PD-L Pathway Beyond Cancer
Qin, W., Hu, L.-P., Zhang, X., Jiang, S., Li, J., Zhang, Z., & Wang, X. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02298 · Cited by 388
“In a report of thyroid disorders, these events occurred when patients with antithyroid antibodies received anti-PD-1 therapy, suggesting that anti-PD-1 treatment may regulate preexisting antithyroid antibodies (178).”
BackgroundZhou, X., Yao, Z., Yang, H., Liang, N., Zhang, X., & Zhang, F. (2020) · BMC Medicine · doi:10.1186/s12916-020-01549-2 · Cited by 368
“Osorio, 2017 [12] NSCLC P 10/48 Thyroid dysfunction 1–3 OS: 0.”
BackgroundToi, Y., Sugawara, S., Sugisaka, J., Ono, H., Kawashima, Y., Aiba, T., Kawana, S., Saito, R., Aso, M., Tsurumi, K., et al. (2019) · JAMA Oncology · doi:10.1001/jamaoncol.2018.5860 · Cited by 352
Toi, Y., Sugawara, S., Kawashima, Y., Aiba, T., Kawana, S., Saito, R., Tsurumi, K., Suzuki, K., Shimizu, H., Sugisaka, J., et al. (2018) · The Oncologist · doi:10.1634/theoncologist.2017-0384 · Cited by 294
“One of these studies reported that among patients with NSCLC treated with pembrolizumab monotherapy, OS was significantly longer in those who developed immune-related thyroid dysfunction than those who did not [19].”
BackgroundImmune-related toxicities of checkpoint inhibitors: mechanisms and mitigation strategies
Sullivan, R. J., & Weber, J. S. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00259-5 · Cited by 312
Delivanis, D. A., Gustafson, M. P., Bornschlegl, S., Merten, M. M., Kottschade, L., Withers, S., Dietz, A. B., & Ryder, M. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-00448 · Cited by 278
“solely serum thyroid antibody measurements (18) and/or results from (18)FDG PET/CT imaging studies (20).”
BackgroundLaumont, C. M., & Nelson, B. H. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.017 · Cited by 269
Autoimmunity, checkpoint inhibitor therapy and immune-related adverse events: A review
Khan, S., & Gerber, D. E. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.06.012 · Cited by 250
“Emerging studies indicate that irAEs represent a consequence of breakdown in self-tolerance mediated at least in part by antigen-specific Tcell responses, autoantibodies, B cells and cytokines [62] [63].”
BackgroundWeinmann, S. C., & Pisetsky, D. S. (2019) · Rheumatology · doi:10.1093/rheumatology/kez308 · Cited by 241
Thyroid Hormones and Cancer: A Comprehensive Review of Preclinical and Clinical Studies
Krashin, E., Piekiełko‐Witkowska, A., Ellis, M. H., & Ashur‐Fabian, O. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00059 · Cited by 228
“In a recent study of 51 non-smallcell lung cancer patients treated with pembrolizumab, a PD1 inhibitor (160), 21% of patients developed hypothyroidism requiring thyroid hormone replacement, with 80% developing positive antithyroid antibodies.”
BackgroundThyroid Immune-related Adverse Events Following Immune Checkpoint Inhibitor Treatment
Muir, C. A., Clifton-Bligh, R. J., Long, G. V., Scolyer, R. A., Lo, S., Carlino, M. S., Tsang, V., & Menzies, A. M. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab263 · Cited by 217
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
“Among patients undergoing pembrolizumab treatment, several cases have been reported to have positive TgAbs or TPOAbs after the development of thyroid dysfunction, some of whom also had them at baseline [18, 19].”
BackgroundHusebye, E. S., Castinetti, F., Criseno, S., Curigliano, G., Decallonne, B., Fleseriu, M., Higham, C., Lupi, I., Paschou, S. Α., Tóth, M., et al. (2022) · European Journal of Endocrinology · doi:10.1530/eje-22-0689 · Cited by 216
Grangeon, M., Tomasini, P., Chaleat, S., Jeanson, A., Souquet-Bressand, M., Khobta, N., Bermudez, J., Trigui, Y., Greillier, L., Blanchon, M., et al. (2018) · Clinical Lung Cancer · doi:10.1016/j.cllc.2018.10.002 · Cited by 205
Immune dysregulation in cancer patients developing immune-related adverse events
Khan, S., Khan, S. A., Luo, X., Fattah, F. J., Saltarski, J., Gloria-McCutchen, Y., Lu, R., Xie, Y., Li, Q., Wakeland, E., et al. (2019) · British Journal of Cancer · doi:10.1038/s41416-018-0155-1 · Cited by 186
New therapeutic perspectives to manage refractory immune checkpoint-related toxicities
Martins, F., Sykiotis, G. P., Maillard, M. H., Fraga, M. C., Ribi, C., Küntzer, T., Michielin, O. A., Peters, S., Coukos, G., Spertini, F., et al. (2019) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30828-3 · Cited by 190
Autoantibody Development under Treatment with Immune-Checkpoint Inhibitors
de Moel, E. C., Rozeman, E. A., Kapiteijn, E. H., Verdegaal, E. M. E., Grummels, A., Bakker, J. A., Huizinga, T. W. J., Haanen, J. B., Toes, R. E. M., & van der Woude, D. (2019) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-18-0245 · Cited by 191
“A relationship between immune-related thyroid dysfunction and clinical outcome has been described previously for various types of cancer immunotherapy, including IL2 (33–35), interferon-2a (35–37), and pembrolizumab (29).”
BackgroundImmune checkpoint inhibitor diabetes mellitus: a novel form of autoimmune diabetes
Quandt, Z., Young, A., & Anderson, M. S. (2020) · Clinical & Experimental Immunology · doi:10.1111/cei.13424 · Cited by 192
Cortellini, A., Chiari, R., Ricciuti, B., Metro, G., Perrone, F., Tiseo, M., Bersanelli, M., Bordi, P., Santini, D., Giusti, R., et al. (2019) · Clinical Lung Cancer · doi:10.1016/j.cllc.2019.02.006 · Cited by 181
Chen, Y., Gao, M., Huang, Z., Yu, J., & Meng, X. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00940-z · Cited by 181
Johnson, D. B., McDonnell, W. J., Gonzalez-Ericsson, P. I., Al-Rohil, R. N., Mobley, B. C., Salem, J.-E., Wang, D. Y., Sanchez, V., Wang, Y., Chastain, C. A., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0523-2 · Cited by 176
Xing, P., Zhang, F., Wang, G., Xu, Y., Li, C., Wang, S., Guo, Y., Cai, S., Wang, Y., & Li, J. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0779-6 · Cited by 181
Tan, M. H., Iyengar, R., Mizokami-Stout, K., Yentz, S., MacEachern, M. P., Shen, L. Y., Redman, B., & Gianchandani, R. (2019) · Clinical Diabetes and Endocrinology · doi:10.1186/s40842-018-0073-4 · Cited by 172
The Balancing Act between Cancer Immunity and Autoimmunity in Response to Immunotherapy
Young, A., Quandt, Z., & Bluestone, J. A. (2018) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-18-0487 · Cited by 170
“Hypothyroidism Autoimmune Autoantibody amplification (6) Hormone replacement Yes (6)”
BackgroundPD-L1 Inhibitor-Induced Thyroiditis Is Associated with Better Overall Survival in Cancer Patients
Kotwal, A., Kottschade, L. A., & Ryder, M. M. (2019) · Thyroid · doi:10.1089/thy.2019.0250 · Cited by 168
“This frequency is slightly lower or similar to the 23–44% reported with PD-1 inhibitor-induced thyroiditis (15,19,20), likely due to the differences in cutoff used for identifying elevated TPO antibodies and the smaller number of patients in our study in whom they were tested.”
BackgroundResultInfluentialKimbara, S., Fujiwara, Y., Iwama, S., Ohashi, K., Kuchiba, A., Arima, H., Yamazaki, N., Kitano, S., Yamamoto, N., & Ohe, Y. (2018) · Cancer Science · doi:10.1111/cas.13800 · Cited by 158
Immune checkpoint inhibitor toxicities
Marin-Acevedo, J. A., Chirila, R. M., & Dronca, R. S. (2019) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2019.03.012 · Cited by 160
Burch, H. B. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1901214 · Cited by 164
A Review of Cancer Immunotherapy Toxicity: Immune Checkpoint Inhibitors
Chhabra, N., & Kennedy, J. M. (2021) · Journal of Medical Toxicology · doi:10.1007/s13181-021-00833-8 · Cited by 155
Fujimoto, D., Yoshioka, H., Kataoka, Y., Morimoto, T., Kim, Y. H., Tomii, K., Ishida, T., Hirabayashi, M., Hara, S., Ishitoko, M., et al. (2018) · Lung Cancer · doi:10.1016/j.lungcan.2018.02.017 · Cited by 147
Owen, D. H., Wei, L., Bertino, E. M., Edd, T., Villalona-Calero, M. A., He, K., Shields, P. G., Carbone, D. P., & Otterson, G. A. (2018) · Clinical Lung Cancer · doi:10.1016/j.cllc.2018.08.008 · Cited by 146
“One retrospective study of 71 patients with NSCLC reported an association between overall response rate and irAEs (P = .007) but not OS (P = .827).9 Another report of 51 patients treated with pembrolizumab in the KEYNOTE-001 trial [study of pembrolizumab (MK-3475) in participants with progressive locally advanced or m…”
BackgroundResultInfluentialFrench Endocrine Society guidance on endocrine side effects of immunotherapy
Castinetti, F., Albarel, F., Archambeaud, F., Bertherat, J., Bouillet, B., Buffier, P., Briet, C., Cariou, B., Caron, P., Chabre, O., et al. (2019) · Endocrine Related Cancer · doi:10.1530/erc-18-0320 · Cited by 140
on behalf of the Italian Nivolumab Renal Cell Cancer Early Access Program group, Verzoni, E., Cartenì, G., Cortesi, E., Giannarelli, D., De Giglio, A., Sabbatini, R., Buti, S., Rossetti, S., Cognetti, F., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0579-z · Cited by 140
Dall’Olio, F. G., Rizzo, A., Mollica, V., Massucci, M., Maggio, I., & Massari, F. (2020) · Immunotherapy · doi:10.2217/imt-2020-0179 · Cited by 140
Safety and Feasibility of Lung Resection After Immunotherapy for Metastatic or Unresectable Tumors
Bott, M. J., Cools‐Lartigue, J., Tan, K. S., Dycoco, J., Bains, M. S., Downey, R. J., Huang, J. G., Isbell, J. M., Molena, D., Park, B. J., et al. (2018) · The Annals of Thoracic Surgery · doi:10.1016/j.athoracsur.2018.02.030 · Cited by 138
Yamauchi, I., Yasoda, A., Matsumoto, S., Sakamori, Y., Kim, Y. H., Nomura, M., Otsuka, A., Yamasaki, T., Saito, R., Kitamura, M., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0216954 · Cited by 137
Adverse Events Associated with Immune Checkpoint Blockade
Tervaert, J.-W. C., Ye, C., & Yacyshyn, E. (2018) · New England Journal of Medicine · doi:10.1056/nejmc1801663 · Cited by 134
Kobayashi, T., Iwama, S., Yasuda, Y., Okada, N., Okuji, T., Ito, M., Onoue, T., Goto, M., Sugiyama, M., Tsunekawa, T., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000779 · Cited by 132
Hypophysitis induced by immune checkpoint inhibitors: a 10-year assessment
Dalmazi, G. D., Ippolito, S., Lupi, I., & Caturegli, P. (2019) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2019.1701434 · Cited by 134
“thyroid antibodies are at much greater risk of developing hypothyroidism after PD-1 blockade than patients who do not have these antibodies at baseline [62].”
BackgroundKim, H. I., Kim, M., Lee, S.-H., Park, S. Y., Kim, Y. N., Kim, H., Jeon, M. J., Kim, T. Y., Kim, S. W., Kim, W. B., et al. (2018) · OncoImmunology · doi:10.1080/2162402x.2017.1375642 · Cited by 123
“pembrolizumab in NSCLC patients was associated with longer OS in an unadjusted analysis.(14) However, to our knowledge, the”
BackgroundPetrelli, F., Grizzi, G., Ghidini, M., Ghidini, A., Ratti, M., Panni, S., Cabiddu, M., Ghilardi, M., Borgonovo, K., Parati, M. C., et al. (2019) · Journal of Immunotherapy · doi:10.1097/cji.0000000000000300 · Cited by 129
Biomarkers of Checkpoint Inhibitor Induced Immune-Related Adverse Events—A Comprehensive Review
Hommes, J. W., Verheijden, R. J., Suijkerbuijk, K. P. M., & Hamann, D. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2020.585311 · Cited by 128
Girotra, M., Hansen, A. R., Farooki, A., Byun, D. J., Min, L., Creelan, B., Callahan, M. K., Atkins, M. B., Sharon, E., Antonia, S. J., et al. (2018) · JNCI Cancer Spectrum · doi:10.1093/jncics/pky021 · Cited by 131
Immune Checkpoint Inhibitor Toxicity
Palmieri, D. J., & Carlino, M. S. (2018) · Current Oncology Reports · doi:10.1007/s11912-018-0718-6 · Cited by 126
Fan, Y., Xie, W., Huang, H., Wang, Y., Li, G., Geng, Y., Hao, Y., & Zhang, Z. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.633032 · Cited by 125
Queirolo, P., Boutros, A., Tanda, E. T., Spagnolo, F., & Quaglino, P. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.08.001 · Cited by 120
Barroso‐Sousa, R., Ott, P. A., Hodi, F. S., Kaiser, U. B., Tolaney, S. M., & Min, L. (2018) · Cancer · doi:10.1002/cncr.31200 · Cited by 122
Preexisting Autoimmune Disease: Implications for Immune Checkpoint Inhibitor Therapy in Solid Tumors
Kennedy, L. C., Bhatia, S., Thompson, J. A., & Grivas, P. D. (2019) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2019.7310 · Cited by 117
Fukihara, J., Sakamoto, K., Koyama, J., Ito, T., Iwano, S., Morise, M., Ogawa, M., Kondoh, Y., Kimura, T., Hashimoto, N., et al. (2019) · Clinical Lung Cancer · doi:10.1016/j.cllc.2019.07.006 · Cited by 114
Ji, H., Tang, X., Dong, Z. W., Song, L., & Jia, Y. (2019) · Clinical Drug Investigation · doi:10.1007/s40261-018-0735-0 · Cited by 113
Thyroid disorders induced by checkpoint inhibitors
Ferrari, S. M., Fallahi, P., Galetta, F., Citi, E., Benvenga, S., & Antonelli, A. (2018) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-018-9463-2 · Cited by 113
“Fifty-one patients with advanced NSCLC were treated with pembrolizumab as part of KEYNOTE-001 (NCT01295827) [70].”
MethodAutoimmune endocrine dysfunctions associated with cancer immunotherapies
Ferrari, S. M., Fallahi, P., Elia, G., Ragusa, F., Ruffilli, I., Patrizio, A., Galdiero, M. R., Baldini, E., Ulisse, S., Marone, G., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20102560 · Cited by 107
“In KEYNOTE–001 (NCT01295827), 51 patients affected by advanced NSCLC received pembrolizumab [64], and their thyroidal function and anti–thyroid antibody serum levels were checked in a prospective manner at each study visit, even prior to the first dose of therapy.”
BackgroundCardiorenal complications of immune checkpoint inhibitors
Sury, K., Perazella, M. A., & Shirali, A. C. (2018) · Nature Reviews Nephrology · doi:10.1038/s41581-018-0035-1 · Cited by 106
Immunotoxicity from checkpoint inhibitor therapy: clinical features and underlying mechanisms
Fessas, P., Possamai, L. A., Clark, J., Daniels, E., Gudd, C. L. C., Mullish, B. H., Alexander, J. L., & Pinato, D. J. (2019) · Immunology · doi:10.1111/imm.13141 · Cited by 106
Management of pulmonary toxicity associated with immune checkpoint inhibitors
Delaunay, M., Prévôt, G., Collot, S., Guilleminault, L., Didier, A. P., & Mazières, J. (2019) · European Respiratory Review · doi:10.1183/16000617.0012-2019 · Cited by 108
Safety and Tolerability of Immune Checkpoint Inhibitors (PD-1 and PD-L1) in Cancer
Baraibar, I., Melero, I., Ponz‐Sarvisé, M., & Álvarez, E. C. (2019) · Drug Safety · doi:10.1007/s40264-018-0774-8 · Cited by 106
Nadal, E., Massutí, B., Dómine, M., García‐Campelo, R., Cobo, M., & Felip, E. (2019) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-019-02310-2 · Cited by 105
Predictive Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Events
Les, I., Martínez, M., Pérez-Francisco, I., Cabero, M., Teijeira, L., Arrazubi, V., Torrego, N., Campillo-Calatayud, A., Elejalde, I., Kochan, G., et al. (2023) · Cancers · doi:10.3390/cancers15051629 · Cited by 100
Kotwal, A., Gustafson, M. P., Bornschlegl, S., Kottschade, L. A., Delivanis, D. A., Dietz, A. B., Gandhi, M. J., & Ryder, M. M. (2020) · Thyroid · doi:10.1089/thy.2020.0075 · Cited by 96
“We (20) and others (4) have shown that patients with thyroid IRAE have better overall survival, suggesting that development of this side effect may be a biomarker of response to ICI therapy in patients with advanced cancer.”
BackgroundCheung, Y.-M. M., Wang, W., McGregor, B. A., & Hamnvik, O. R. (2022) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-021-03128-7 · Cited by 101
Ahn, B., Pyo, K., Xin, C.-F., Jung, D., Shim, H. S., Lee, C. Y., Park, S. Y., Yoon, H. I., Hong, M. H., Cho, B. C., et al. (2019) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-019-02899-y · Cited by 95
Iranzo, P., Callejo, A., Assaf, J. D., Molina, G., López-Valbuena, D., García-Illescas, D., Pardo, N., Navarro, A., Martínez‐Martí, A., Cedrés, S., et al. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.875974 · Cited by 102
“study of patients treated with pembrolizumab showed that, up to 80% of patients who developed hypothyroidism had antithyroid antibodies compared with 8% of patients with normal thyroid function (18).”
BackgroundTocchetti, C. G., Farmakis, D. T., Koop, Y., Andrés, M. S., Couch, L. S., Formisano, L., Ciardiello, F., Pane, F., Au, L., Emmerich, M., et al. (2024) · European Journal of Heart Failure · doi:10.1002/ejhf.3340 · Cited by 102
Immunotherapy toxicity: identification and management
Gumusay, O., Callan, J., & Rugo, H. S. (2022) · Breast Cancer Research and Treatment · doi:10.1007/s10549-021-06480-5 · Cited by 98
“One possible explanation of this phenomenon is that anti-PD-1 and anti-PD-L1 treatments, in addition to providing T-cell-mediated immunity, modulate humoral immunity and thereby enhance pre-existing antithyroid antibodies [12].”
BackgroundIshihara, H., Takagi, T., Kondo, T., Homma, C., Tachibana, H., Fukuda, H., Yoshida, K., Iizuka, J., Kobayashi, H., Okumi, M., et al. (2019) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/j.urolonc.2019.03.003 · Cited by 91
Basak, E. A., van der Meer, J. W. M., Hurkmans, D. P., Schreurs, M. W. J., Hoop, E. O., van der Veldt, A. A. M., Bins, S., Joosse, A., Koolen, S. L. W., Debets, R., et al. (2020) · Thyroid · doi:10.1089/thy.2019.0726 · Cited by 92
“…that thyroid toxicity during anti-PD-1 treat-ment may be associated with improved overall survival (OS), but these studies were limited by small sample sizes, including only patients with nonsmall-cell lung carcinoma (NSCLC), and showed inconsistent effects on progression-free survival (PFS) (6,7).”
Casagrande, S., Sopetto, G. B., Bertalot, G., Bortolotti, R., Racanelli, V., Caffo, O., Giometto, B., Berti, A., & Veccia, A. (2024) · Cancers · doi:10.3390/cancers16071440 · Cited by 99
“This is the case of ICI-induced thyroid dysfunction, which was observed in patients with higher titers of anti-thyroid autoAbs [64].”
BackgroundIsolated ACTH deficiency induced by cancer immunotherapy: a systematic review
Iglesias, P., Sánchez, J. C., & Díez, J. J. (2021) · Pituitary · doi:10.1007/s11102-021-01141-8 · Cited by 90
Yasuda, Y., Iwama, S., Sugiyama, D., Okuji, T., Kobayashi, T., Ito, M., Okada, N., Enomoto, A., Ito, S., Yan, Y., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abb7495 · Cited by 86
“(39) reported that the prevalence of anti-thyroid antibodies (TgAb or anti-microsomal antibodies) during the observational period was higher in patients with versus those without thyroid-irAE (8 of 10 versus 3 of 38).”
BackgroundKhan, Z., Hammer, C., Carroll, J., Nucci, F. D., Acosta, S. L., Maiya, V., Bhangale, T., Hunkapiller, J., Mellman, I., Albert, M. L., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23661-4 · Cited by 83
Ksienski, D., Wai, E. S., Croteau, N. S., Fiorino, L., Brooks, E., Poonja, Z., Fenton, D., Geller, G., Glick, D., & Lesperance, M. (2018) · Clinical Lung Cancer · doi:10.1016/j.cllc.2018.09.005 · Cited by 86
Ibis, B., Aliazis, K., Cao, C., Yenyuwadee, S., & Boussiotis, V. A. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1197364 · Cited by 92
Luo, J., Martucci, V. L., Quandt, Z., Groha, S., Murray, M. H., Lovly, C. M., Rizvi, H. A., Egger, J. V., Plodkowski, A. J., Abu-Akeel, M., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-0921 · Cited by 85
Inflammatory and Infectious Syndromes Associated With Cancer Immunotherapies
Fishman, J. A., Hogan, J. I., & Maus, M. V. (2018) · Clinical Infectious Diseases · doi:10.1093/cid/ciy1025 · Cited by 83
“Patients develop constitutional symptoms (ie, fatigue, myalgias, dizziness, nausea) with thyroid dysfunction; hypothyroidism, often with antithyroid antibodies, is more common than hyperthyroidism [40].”
BackgroundImmune-related adverse events: promising predictors for efficacy of immune checkpoint inhibitors
Zhong, L., Wu, Q., Chen, F., Liu, J., & Xie, X. (2021) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-020-02803-5 · Cited by 87
Thyroid dysfunctions secondary to cancer immunotherapy
Chalan, P., Dalmazi, G. D., Pani, F., Remigis, A. D., Corsello, A., & Caturegli, P. (2017) · Journal of Endocrinological Investigation · doi:10.1007/s40618-017-0778-8 · Cited by 83
Thyroid Toxicity Following Immune Checkpoint Inhibitor Treatment in Advanced Cancer
Muir, C. A., Menzies, A. M., Clifton-Bligh, R. J., & Tsang, V. (2020) · Thyroid · doi:10.1089/thy.2020.0032 · Cited by 82
“Others have re-ported increased prevalence of antithyroid antibodies in cases of thyroid irAEs relative to controls unaffected by thyroid dysfunction (58,84–86).”
InfluentialPredictive Biomarkers of Immune Checkpoint Inhibitors-Related Toxicities
Xu, Y., Fu, Y., Zhu, B., Wang, J., & Zhang, B. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.02023 · Cited by 83
“Compared with those patients free of thyroiditis, the baseline anti-thyroglobulin antibodies (TgAbs) and anti-thyroid peroxidase antibodies (TPOAbs) levels were significantly higher in destructive thyroiditis patients (41), the appearance of thyroid dysfunction during PD-1 treatment closely associated with anti-thyroi…”
BackgroundImpact of Glucocorticoid Use in Oncology in the Immunotherapy Era
Kalfeist, L., Galland, L., Ledys, F., Ghiringhelli, F., Limagne, E., & Ladoire, S. (2022) · Cells · doi:10.3390/cells11050770 · Cited by 78
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
Passat, T., Touchefeu, Y., Gervois, N., Jarry, A., Bossard, C., & Bennouna, J. (2018) · Bulletin du Cancer · doi:10.1016/j.bulcan.2018.07.005 · Cited by 78
“rant l'influence potentielle des ICPI sur l'immunité humorale [30].”
BackgroundImmune Checkpoint Inhibitor-Induced Hypophysitis and Patterns of Loss of Pituitary Function
Jessel, S., Weiss, S. A., Austin, M., Mahajan, A. K., Etts, K., Zhang, L., Aizenbud, L., Perdigoto, A. L., Hurwitz, M. E., Sznol, M., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.836859 · Cited by 79
Immune checkpoint inhibitor-related pneumonitis: research advances in prediction and management
Lin, M., Zang, D., Liu, C., Han, X., & Chen, J. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1266850 · Cited by 79
Rivero, J. D., Cordes, L. M., Kłubo-Gwieździńska, J., Madan, R. A., Nieman, L. K., & Gulley, J. L. (2019) · The Oncologist · doi:10.1634/theoncologist.2018-0470 · Cited by 79
Gastrointestinal adverse events associated with immune checkpoint inhibitor therapy
Rajha, E., Chaftari, P. S., Kamal, M. J., Maamari, J., Chaftari, C. P., & Yeung, S. J. (2019) · Gastroenterology report · doi:10.1093/gastro/goz065 · Cited by 76
Immune checkpoint inhibitor-related thyroid dysfunction
Iwama, S., Kobayashi, T., Yasuda, Y., & Arima, H. (2022) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2022.101660 · Cited by 76
Tyrosine kinase inhibitors and immune checkpoint inhibitors-induced thyroid disorders
Jannin, A., Penel, N., Ladsous, M., Vantyghem, M., & Cao, C. D. (2019) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2019.05.015 · Cited by 77
Metadata
- Authors
- Osorio, J. C., Ni, A., Chaft, J. E., Pollina, R., Kasler, M. K., Stephens, D., Rodriguez, C., Cambridge, L., Rizvi, H., Wolchok, J. D., Merghoub, T., Rudin, C. M., Fish, S., & Hellmann, M. D.
- Affiliations
- Weill Cornell Medicine (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Hellmann, M.D.
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 28
- Issue
- 3
- Pages
- 583-589
- ISSN
- 0923-7534 (ISSN-L)
- PMC
- PMC5834017
- OpenAlex
- W2561156916
- Cited by
- 659
- References
- 26
- Citations by year
- 2026: 23 · 2025: 50 · 2024: 70 · 2023: 75 · 2022: 102 · 2021: 95 · 2020: 98 · 2019: 77 · 2018: 51 · 2017: 17
- FWCI
- 26.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (P30 CA008748)
- Fiona and Stanley Druckenmiller Center for Lung Cancer Research
- KEYNOTE-001 (NCT01295827)
- Merck Sharp & Dohme, a subsidiary of Merck
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Clinical Neurology › Autoimmune Neurological Disorders and Treatments
- Keywords
- immune-related adverse events, anti-thyroid antibodies, pembrolizumab, anti-PD-1 therapy, non-small cell lung cancer, hypothyroidism, hyperthyroidism, humoral immunity, immune checkpoint inhibitors, progression-free survival, overall survival
- MeSH terms
- Adolescent, Adult, Aged, Antibodies, Monoclonal, Carcinoma, Non-Small-Cell Lung, Female, Humans, Hyperthyroidism, Male, Middle Aged, Neoplasm Staging, T-Lymphocytes, Thyroid Gland, Disease-Free Survival, Programmed Cell Death 1 Receptor, Antibodies, Monoclonal, Humanized, Drug-Related Side Effects and Adverse Reactions
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