THYROID DYSFUNCTIONS INDUCED BY IMMUNE CHECK-POINT INHIBITORS
Keywords:immune check-point inhibitors, thyroid side effects, anti-CTLA-4, anti-PD-1, anti-PD-L-1 monoclonal antibodies
The immune system is the core defense against cancer development and progression. Failure of the immune system to recognize and eliminate malignant cells plays an immense role in the pathogenesis of cancer. The paramount achievement in immunotherapy particularly – Immune Check-point Inhibitors (ICI) over the recent decade has brought about major paradigm shift in cancer treatment. ICIs, represented mainly by inhibitory monoclonal antibodies – anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) (ipilimumab), anti-programmed cell death protein 1 (PD-1-pembrolizumab/nivolumab/cemiplimab), Anti-PD-1 Ligand molecules (PD-L-1- atezolizumab/avelumab/durvalumab) reactivate the immune system against tumor cells but can also trigger a myriad of autoimmune side effects, termed immune-related adverse events (irAEs). Immunotherapy related adverse events typically have a delayed onset and prolonged duration compared to adverse events from chemotherapy, and its effective management depends on early recognition and prompt intervention with immune suppression and/or immunomodulatory strategies.The present review aims to raise awareness about thyroid side effects of immune check-point inhibitors to physicians who are taking care of cancer patients and to specialists - mainly oncologists and endocrinologists who are urged to cooperate for the management of thyroid immunotoxicity.
Marin-Acevedo, J.A., Kimbrough, E.O. & Lou, Y. Next generation of immune checkpoint inhibitors and beyond. J Hematol Oncol 14, 45 (2021). https://doi.org/10.1186/s13045-021-01056-8
Puzanov, I., Diab, A., Abdallah, K. et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. j. immunotherapy cancer 5, 95(2017). https://doi.org/10.1186/s40425-017-0300-z
Ferrari SM, Fallahi P, Galetta F, Citi E, Benvenga S, Antonelli A. Thyroid disorders induced by checkpoint inhibitors. Rev Endocr Metab Disord. 2018 Dec;19(4):325-333. doi: 10.1007/s11154-018-9463-2. PMID: 30242549.
Momtaz P, Postow MA. Immunologic checkpoints in cancer therapy: focus on the programmed death-1 (PD-1) receptor pathway. Pharmgenomics Pers Med. 2014 Nov 15;7:357-65. doi: 10.2147/PGPM.S53163. PMID: 25484597; PMCID: PMC4238865.
El Sabbagh R, Azar NS, Eid AA, Azar ST. Thyroid Dysfunctions Due to Immune Checkpoint Inhibitors: A Review. Int J Gen Med. 2020;13:1003-1009 https://doi.org/10.2147/IJGM.S261433
Hansen D.E , Wang X, Case A.A, Puzanov I and Smith T. Immune Checkpoint Inhibitor Toxicity Review for the Palliative Care Clinician. 2018 May 21;DOI:https://doi.org/10.1016/j.jpainsymman.2018.05.015
Cukier P., Santini F. C., Scaranti M., & Hoff A. O. (2017). Endocrine side effects of cancer immunotherapy, Endocrine-Related Cancer, 24(12), T331-T347. Retrieved Dec 3, 2021, from https://erc.bioscientifica.com/view/journals/erc/24/12/ERC-17-0358.xml
Joshi B.C. Whitelaw M.T.P et al., Immune checkpoint inhibitor-related hypophysitis and endocrine dysfunction: clinical review. 2016 March 21 https://doi.org/10.1111/cen.13063
Khan S, Gerber DE. Autoimmunity, checkpoint inhibitor therapy and immune-related adverse events: A review. Semin Cancer Biol. 2020 Aug;64:93-101. doi: 10.1016/j.semcancer.2019.06.012. Epub 2019 Jul 19. PMID: 31330185; PMCID: PMC6980444.
Romualdo Barroso-Sousa, Patrick A. Ott, F. Stephen Hodi et al., Endocrine dysfunction induced by immune checkpoint inhibitors: Practical recommendations for diagnosis and clinical management. 2018 Jan 03; https://doi.org/10.1002/cncr.31200
Deligiorgi M, Mihalis I Panayiotidis & Dimitrios T Trafalis. Endocrine adverse events related with immune checkpoint inhibitors: an update for clinicians. 2020 Apr 29; https://doi.org/1s0.2217/imt-2019-0132
Delivanis DA, Gustafson MP, Bornschlegl S, et al. Pembrolizumab-Induced Thyroiditis: Comprehensive Clinical Review and Insights Into Underlying Involved Mechanisms. J Clin Endocrinol Metab. 2017;102(8):2770-2780. doi:10.1210/jc.2017-00448
Zhan Ling, Feng Hong-fang, Liu Han-qing, Guo Lian-tao, Chen Chuang, Yao Xiao-li, Sun Sheng-rong. Immune Checkpoint Inhibitors-Related Thyroid Dysfunction: Epidemiology, Clinical Presentation, Possible Pathogenesis, and Management. 2021 Jun 10; https://doi.org/10.3389/fendo.2021.649863
Peiffert M, Cugnet-Anceau Ch , Dalle S , Chikh K , Assaad S , Disse E , Raverot G. Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review); 2021 Apr 17; doi:10.3390/cancers13081944
Kumar V, Chaudhary N, Garg M, Floudas CS, Soni P, Chandra AB. Current Diagnosis and Management of Immune Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitor Therapy. Front Pharmacol. 2017 Feb 8;8:49. doi: 10.3389/fphar.2017.00049. Erratum in: Front Pharmacol. 2017 May 31;8:311. PMID: 28228726; PMCID: PMC5296331.
Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA; National Comprehensive Cancer Network. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018 Jun 10;36(17):1714-1768. doi: 10.1200/JCO.2017.77.6385. Epub 2018 Feb 14. PMID: 29442540; PMCID: PMC6481621.
Brahmer JR, Abu-Sbeih H, Ascierto PA, Brufsky J, Cappelli LC, Cortazar FB, Gerber DE, Hamad L, Hansen E, Johnson DB, Lacouture ME, Masters GA, Naidoo J, Nanni M, Perales MA, Puzanov I, Santomasso BD, Shanbhag SP, Sharma R, Skondra D, Sosman JA, Turner M, Ernstoff MS. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events. J Immunother Cancer. 2021 Jun;9(6):e002435. doi: 10.1136/jitc-2021-002435. PMID: 34172516; PMCID: PMC8237720.
Sznola M, A.Postowbc M, J.Daviesd M, C.Pavlicke A, R.Plimackf E, Shaheeng M, Veloskif C, Roberth C. Endocrine-related adverse events associated with immune checkpoint blockade and expert insights on their management. 2017 Jul; https://doi.org/10.1016/j.ctrv.2017.06.002
Vajaitu C, Draghici CC, Solomon I, et al. The Central Role of Inflammation Associated with Checkpoint Inhibitor Treatments. J Immunol Res. 2018;2018:4625472. Published 2018 Oct 17. doi:10.1155/2018/4625472