tumorsMalignant tumoursMalignant tumours2224-50572587-6813Rosoncoweb10.18027/2224-5057-2024-14-3s1-53-62tumors-1348Research ArticleСтатьиРедкие иммуноопосредованные нежелательные явления: клиническая характеристика, подходы к диагностике и лечениюhttps://orcid.org/0000-0003-4848-6938ЖуковаЛ. Г.

Жукова Людмила Григорьевна

111123 Москва, ул. Новогиреевская, 1, корп. 1

https://orcid.org/0009-0002-8509-5944ПасечнюкО. С.

Пасечнюк Ольга Сергеевна

111123 Москва, ул. Новогиреевская, 1, корп. 1

https://orcid.org/0000-0001-5417-0425ПольшинаН. И.

Польшина Наталья Ивановна

111123 Москва, ул. Новогиреевская, 1, корп. 1

https://orcid.org/0009-0002-4945-9181ХачатурянЭ. А.

Хачатурян Элина Артуровна

117152 Москва, Загородное ш., 18А, стр. 7

https://orcid.org/0000-0002-0616-5477ГречухинаК. С.

Катерина Сергеевна Гречухина 

111123 Москва, ул. Новогиреевская, 1, корп. 1

k.grechukhina@mknc.ruГБУЗ «Московский клинический научный центр имени А. С. Логинова Департамента здравоохранения города Москвы»Russian FederationГБУЗ «Онкологический центр № 1 Городской клинической больницы имени С. С. Юдина Департамента здравоохранения города Москвы»Russian Federation202418112024143s15362Copyright © Жукова Л.Г., Пасечнюк О.С., Польшина Н.И., Хачатурян Э.А., Гречухина К.С., 20242024Жукова Л.Г., Пасечнюк О.С., Польшина Н.И., Хачатурян Э.А., Гречухина К.С.Жукова Л.Г., Пасечнюк О.С., Польшина Н.И., Хачатурян Э.А., Гречухина К.С.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.malignanttumors.org/jour/article/view/1348

Внедрение иммунотерапии позволило при ряде злокачественных опухолей (ЗНО) значимо увеличить продолжительность жизни пациентов в сравнении с «классической» химиотерапией. Способность иммунотерапевтических препаратов активировать Т-лимфоциты позволяет, с одной стороны, добиться противоопухолевого эффекта, с другой — может приводить к развитию иммуноопосредованных нежелательных явлений (иоНЯ). Наиболее распространенными иоНЯ являются эндокринные (гипо- или гипертиреоз), гастроинтестинальные (колит, гепатит) и дерматологические (зуд, сыпь) реакции. Редкие, но потенциально угрожающие жизни иоНЯ требуют особого внимания.

Особое место занимает перекрестный синдром, включающий миокардит, миастению и миозит, который отличается быстрыми темпами прогрессирования и высокой летальностью. Миокардит проявляется болями в груди, одышкой и тахикардией, с повышением уровня тропонина — важного диагностического маркера. Сопутствующие миозит и миастения гравис проявляются миалгией и слабостью конечностей. Для разрешения этих иоНЯ требуется применение высоких доз глюкокортикостероидов (ГКС) и иногда плазмафереза.

Среди неврологических иоНЯ особо выделяют энцефалит и синдром Гийена-Барре. Энцефалит проявляется различными общемозговыми симптомами: изменениями психического статуса, головной болью, судорогами и т. д. Синдром Гийена-Барре при этом проявляется мышечной слабостью и парестезиями. Диагностика включает люмбальную пункцию, электроэнцефалограмму и ряд лабораторных исследований. Лечение основано на высоких дозах ГКС, при резистентности к ГКС — использование ритуксимаба.

Офтальмологические иоНЯ могут проявляться сухостью глаз, увеитом и невритом зрительного нерва, иногда приводя к серозной отслойке сетчатки. Для диагностики требуется доступность узкоспециализированных методов, таких как офтальмоскопия и оптическая когерентная томография. Лечение включает топические и местные инъекционные ГКС.

Редкие иоНЯ подчеркивают необходимость междисциплинарного подхода в лечении ЗНО, учитывая сложности диагностики и ведения подобных пациентов. Эта проблема становится все более актуальной с расширением показаний к применению иммунотерапии, что требует разработки эффективных методов управления этими особыми и иногда фатальными осложнениями.

иммунотерапиянежелательные явленияиммуноопосредованные нежелательные явленияReferencesDarnell E.P., Mooradian M.J., Baruch E.N. et.al. Immune-Related Adverse Events (irAEs): Diagnosis, Management, and Clinical Pearls. Curr Oncol Rep 2020;22(4):39–39. https://doi.org/10.1007/S11912-020-0897-9Darnell E.P., Mooradian M.J., Baruch E.N. et.al. Immune-Related Adverse Events (irAEs): Diagnosis, Management, and Clinical Pearls. Curr Oncol Rep 2020;22(4):39–39. https://doi.org/10.1007/S11912-020-0897-9Francisco L.M., Salinas V.H., Brown K.E., et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med 2009;206(13):3015–29. https://doi.org/10.1084/JEM.20090847Francisco L.M., Salinas V.H., Brown K.E., et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med 2009;206(13):3015–29. https://doi.org/10.1084/JEM.20090847Amarnath S., Mangus C.W., Wang J.C.M., et al. The PDL1-PD1 Axis Converts Human Th1 Cells Into Regulatory T Cells. Sci Transl Med 2011;3(111):111ra120. https://doi.org/10.1126/SCITRANSLMED.3003130Amarnath S., Mangus C.W., Wang J.C.M., et al. The PDL1-PD1 Axis Converts Human Th1 Cells Into Regulatory T Cells. Sci Transl Med 2011;3(111):111ra120. https://doi.org/10.1126/SCITRANSLMED.3003130Vaddepally R., Doddamani R., Sodavarapu S., et al. Review of Immune-Related Adverse Events (irAEs) in Non-Small-Cell Lung Cancer (NSCLC)-Their Incidence, Management, Multiorgan irAEs, and Rechallenge. Biomedicines 2022;10(4):790. https://doi.org/10.3390/BIOMEDICINES10040790Vaddepally R., Doddamani R., Sodavarapu S., et al. Review of Immune-Related Adverse Events (irAEs) in Non-Small-Cell Lung Cancer (NSCLC)-Their Incidence, Management, Multiorgan irAEs, and Rechallenge. Biomedicines 2022;10(4):790. https://doi.org/10.3390/BIOMEDICINES10040790Abdel-Wahab N., Diab A., Yu R.K., et al. Genetic determinants of immune-related adverse events in patients with melanoma receiving immune checkpoint inhibitors. Cancer Immunol Immunother 2021;70(7):1939–49. https://doi.org/10.1007/S00262-020-02797-0Abdel-Wahab N., Diab A., Yu R.K., et al. Genetic determinants of immune-related adverse events in patients with melanoma receiving immune checkpoint inhibitors. Cancer Immunol Immunother 2021;70(7):1939–49. https://doi.org/10.1007/S00262-020-02797-0Nishino M., Ramaiya N.H., Awad M.M., et al. PD-1 Inhibitor-Related Pneumonitis in Advanced Cancer Patients: Radiographic Patterns and Clinical Course. Clin Cancer Res 2016;22(24):6051–60. https://doi.org/10.1158/1078-0432.Nishino M., Ramaiya N.H., Awad M.M., et al. PD-1 Inhibitor-Related Pneumonitis in Advanced Cancer Patients: Radiographic Patterns and Clinical Course. Clin Cancer Res 2016;22(24):6051–60. https://doi.org/10.1158/1078-0432.Delaunay M., Cadranel J., Lusque A., et al. Immune-checkpoint inhibitors associated with interstitial lung disease in cancer patients. Eur Respir J 2017;50(2):1700050. https://doi.org/10.1183/13993003.00050-2017Delaunay M., Cadranel J., Lusque A., et al. Immune-checkpoint inhibitors associated with interstitial lung disease in cancer patients. Eur Respir J 2017;50(2):1700050. https://doi.org/10.1183/13993003.00050-2017Naidoo J., Wang X., Woo K.M., et al. Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy. J Clin Oncol 2017;35(7):709–717. https://doi.org/10.1200/JCO.2016.68.2005Naidoo J., Wang X., Woo K.M., et al. Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy. J Clin Oncol 2017;35(7):709–717. https://doi.org/10.1200/JCO.2016.68.2005Weber J.S., Kähler K.C., Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol 2012;30(21):2691–7. https://doi.org/10.1200/JCO.2012.41.6750Weber J.S., Kähler K.C., Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol 2012;30(21):2691–7. https://doi.org/10.1200/JCO.2012.41.6750Gettinger S.N., Horn L., Gandhi L., et al. Overall Survival and Long-Term Safety of Nivolumab (Anti–Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer. J Clin Oncol 2015;33(18):2004–12. https://doi.org/10.1200/JCO.2014.58.3708Gettinger S.N., Horn L., Gandhi L., et al. Overall Survival and Long-Term Safety of Nivolumab (Anti–Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer. J Clin Oncol 2015;33(18):2004–12. https://doi.org/10.1200/JCO.2014.58.3708Schoenfeld S.R., Aronow M.E., Leaf R.K., et al. Diagnosis and Management of Rare Immune-Related Adverse Events. Oncologist 2020;25(1):6–14. https://doi.org/10.1634/theoncologist.2019-0083Schoenfeld S.R., Aronow M.E., Leaf R.K., et al. Diagnosis and Management of Rare Immune-Related Adverse Events. Oncologist 2020;25(1):6–14. https://doi.org/10.1634/theoncologist.2019-0083Puzanov 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 Immunother Cancer 2017;5(1):95. https://doi.org/10.1186/S40425-017-0300-ZPuzanov 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 Immunother Cancer 2017;5(1):95. https://doi.org/10.1186/S40425-017-0300-ZBrahmer J.R., Lacchetti C., Schneider B.J., et al. 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;36(17):1714–68. https://doi.org/10.1200/JCO.2017.77.6385Brahmer J.R., Lacchetti C., Schneider B.J., et al. 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;36(17):1714–68. https://doi.org/10.1200/JCO.2017.77.6385Kuusisalo S., Koivunen J.P., Iivanainen S. Association of Rare Immune-Related Adverse Events to Survival in Advanced Cancer Patients Treated with Immune Checkpoint Inhibitors: A Real-World Single-Center Cohort Study. Cancers (Basel) 2022;14(9):2276. https://doi.org/10.3390/cancers14092276Kuusisalo S., Koivunen J.P., Iivanainen S. Association of Rare Immune-Related Adverse Events to Survival in Advanced Cancer Patients Treated with Immune Checkpoint Inhibitors: A Real-World Single-Center Cohort Study. Cancers (Basel) 2022;14(9):2276. https://doi.org/10.3390/cancers14092276Moslehi J.J., Salem J.E., Sosman J.A., et al. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet 2018;391(10124):933. https://doi.org/10.1016/S0140-6736(18)30533-6Moslehi J.J., Salem J.E., Sosman J.A., et al. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet 2018;391(10124):933. https://doi.org/10.1016/S0140-6736(18)30533-6Wang D.Y., Salem J.E., Cohen J.V., et al. Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis. JAMA Oncol 2018;4(12):1721–8. https://doi.org/10.1001/jamaoncol.2018.3923Wang D.Y., Salem J.E., Cohen J.V., et al. Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis. JAMA Oncol 2018;4(12):1721–8. https://doi.org/10.1001/jamaoncol.2018.3923Park B.C., Narayanan S., Gavraldis A., et al. Rare immune-related adverse events in patients with melanoma: incidence, spectrum, and clinical presentations. Oncoimmunology 2023;12(1):2188719. https://doi.org/10.1080/2162402X.2023.2188719Park B.C., Narayanan S., Gavraldis A., et al. Rare immune-related adverse events in patients with melanoma: incidence, spectrum, and clinical presentations. Oncoimmunology 2023;12(1):2188719. https://doi.org/10.1080/2162402X.2023.2188719Javaid A., Bennett C., Rao A., Spain L. Rare Immune-Related Adverse Events (irAEs): Approach to Diagnosis and Management. Pharmaceut Med 2024;38(1):25–38. https://doi.org/10.1007/S40290-023-00508-5Javaid A., Bennett C., Rao A., Spain L. Rare Immune-Related Adverse Events (irAEs): Approach to Diagnosis and Management. Pharmaceut Med 2024;38(1):25–38. https://doi.org/10.1007/S40290-023-00508-5Haanen J., Obeid M., Spain L., et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2022;33(12):1217–38. https://doi.org/10.1016/J.annonc.2022.10.001Haanen J., Obeid M., Spain L., et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2022;33(12):1217–38. https://doi.org/10.1016/J.annonc.2022.10.001Palaskas N., Lopez-Mattei J., Durand J.B., et al. Immune Checkpoint Inhibitor Myocarditis: Pathophysiological Characteristics, Diagnosis, and Treatment. J Am Heart Assoc 2020;9(2):e013757. https://doi.org/10.1161/JAHA.119.013757Palaskas N., Lopez-Mattei J., Durand J.B., et al. Immune Checkpoint Inhibitor Myocarditis: Pathophysiological Characteristics, Diagnosis, and Treatment. J Am Heart Assoc 2020;9(2):e013757. https://doi.org/10.1161/JAHA.119.013757Brahmer J.R., Lacchetti C., Schneider B.J., et al. 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;36(17):1714–68. https://doi.org/10.1200/JCO.2017.77.6385Brahmer J.R., Lacchetti C., Schneider B.J., et al. 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;36(17):1714–68. https://doi.org/10.1200/JCO.2017.77.6385Mahmood S.S., Fradley M.G., Cohen J.V., et al. Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol 2018;71(16):A699. https://doi.org/10.1016/S0735-1097(18)31240-3Mahmood S.S., Fradley M.G., Cohen J.V., et al. Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol 2018;71(16):A699. https://doi.org/10.1016/S0735-1097(18)31240-3Herrmann J., Lenihan D., Armenian S., et al. Defining cardiovascular toxicities of cancer therapies: an International Cardio-Oncology Society (IC-OS) consensus statement. Eur Heart J 2022;43(4):280–99. https://doi.org/10.1093/eurheartj/ehab674Herrmann J., Lenihan D., Armenian S., et al. Defining cardiovascular toxicities of cancer therapies: an International Cardio-Oncology Society (IC-OS) consensus statement. Eur Heart J 2022;43(4):280–99. https://doi.org/10.1093/eurheartj/ehab674Nelke C., Pawlitzki M., Kerkhoff R., et al. Immune Checkpoint Inhibition-Related Myasthenia-Myositis-Myocarditis Responsive to Complement Blockade. Neurol Neuroimmunol Neuroinflamm 2023;11(1):e200177. https://doi.org/10.1212/NXI.0000000000200177Nelke C., Pawlitzki M., Kerkhoff R., et al. Immune Checkpoint Inhibition-Related Myasthenia-Myositis-Myocarditis Responsive to Complement Blockade. Neurol Neuroimmunol Neuroinflamm 2023;11(1):e200177. https://doi.org/10.1212/NXI.0000000000200177Albarrán-Artahona V., Laguna J.C., Gorría T., et al. Immune-Related Uncommon Adverse Events in Patients with Cancer Treated with Immunotherapy. Diagnostics (Basel) 2022;12(9):2091. https://doi.org/10.3390/diagnostics12092091Albarrán-Artahona V., Laguna J.C., Gorría T., et al. Immune-Related Uncommon Adverse Events in Patients with Cancer Treated with Immunotherapy. Diagnostics (Basel) 2022;12(9):2091. https://doi.org/10.3390/diagnostics12092091Huang Y.T., Chen Y.P., Lin W.C., et al. Immune Checkpoint Inhibitor-Induced Myasthenia Gravis. Front Neurol 2020;11:528324. https://doi.org/10.3389/fneur.2020.00634/bibtexHuang Y.T., Chen Y.P., Lin W.C., et al. Immune Checkpoint Inhibitor-Induced Myasthenia Gravis. Front Neurol 2020;11:528324. https://doi.org/10.3389/fneur.2020.00634/bibtexLarkin J., Chmielowski B., Lao C.D., et al. Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis. Oncologist 2017;22(6):709–718. https://doi.org/10.1634/theoncologist.2016-0487Larkin J., Chmielowski B., Lao C.D., et al. Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis. Oncologist 2017;22(6):709–718. https://doi.org/10.1634/theoncologist.2016-0487Kao J.C., Brickshawana A., Liewluck T. Neuromuscular Complications of Programmed Cell Death-1 (PD-1) Inhibitors. Curr Neurol Neurosci Rep 2018;18(10):63. https://doi.org/10.1007/S11910-018-0878-7Kao J.C., Brickshawana A., Liewluck T. Neuromuscular Complications of Programmed Cell Death-1 (PD-1) Inhibitors. Curr Neurol Neurosci Rep 2018;18(10):63. https://doi.org/10.1007/S11910-018-0878-7Marini A., Bernardini A., Gigli G.L., et al. Neurologic Adverse Events of Immune Checkpoint Inhibitors: A Systematic Review. Neurology 2021;96(16):754–66. https://doi.org/10.1212/WNL.0000000000011795Marini A., Bernardini A., Gigli G.L., et al. Neurologic Adverse Events of Immune Checkpoint Inhibitors: A Systematic Review. Neurology 2021;96(16):754–66. https://doi.org/10.1212/WNL.0000000000011795Thouvenin L ., Olivier T., Banna G., et al. Immune checkpoint inhibitor-induced aseptic meningitis and encephalitis: a case-series and narrative review. Ther Adv Drug Saf 2021;12:20420986211004745. https://doi.org/10.1177/20420986211004745Thouvenin L ., Olivier T., Banna G., et al. Immune checkpoint inhibitor-induced aseptic meningitis and encephalitis: a case-series and narrative review. Ther Adv Drug Saf 2021;12:20420986211004745. https://doi.org/10.1177/20420986211004745Müller-Jensen L., Zierold S., Versluis J.M., et al. Characteristics of immune checkpoint inhibitor-induced encephalitis and comparison with HSV-1 and anti-LGI1 encephalitis: A retrospective multicentre cohort study. Eur J Cancer 2022;175:224–235. https://doi.org/10.1016/J.EJCA.2022.08.009Müller-Jensen L., Zierold S., Versluis J.M., et al. Characteristics of immune checkpoint inhibitor-induced encephalitis and comparison with HSV-1 and anti-LGI1 encephalitis: A retrospective multicentre cohort study. Eur J Cancer 2022;175:224–235. https://doi.org/10.1016/J.EJCA.2022.08.009Dubey D., David W.S., Reynolds K.L., et al. Severe Neurological Toxicity of Immune Checkpoint Inhibitors: Growing Spectrum. Ann Neurol 2020;87(5):659–669. https://doi.org/10.1002/ANA.25708Dubey D., David W.S., Reynolds K.L., et al. Severe Neurological Toxicity of Immune Checkpoint Inhibitors: Growing Spectrum. Ann Neurol 2020;87(5):659–669. https://doi.org/10.1002/ANA.25708Velasco R., Villagrán M., Jové M., et al. Encephalitis Induced by Immune Checkpoint Inhibitors: A Systematic Review. JAMA Neurol 2021;78(7):864–873. https://doi.org/10.1001/jamaneurol.2021.0249Velasco R., Villagrán M., Jové M., et al. Encephalitis Induced by Immune Checkpoint Inhibitors: A Systematic Review. JAMA Neurol 2021;78(7):864–873. https://doi.org/10.1001/jamaneurol.2021.0249Johnson D.B., Manouchehri A., Haugh A.M., et al. Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study. J Immunother Cancer 2019;7(1):134. https://doi.org/10.1186/S40425-019-0617-XJohnson D.B., Manouchehri A., Haugh A.M., et al. Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study. J Immunother Cancer 2019;7(1):134. https://doi.org/10.1186/S40425-019-0617-XMartins F., Sofiya L., Sykiotis G.P., et al. Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat Rev Clin Oncol 2019;16(9):563–580. https://doi.org/10.1038/S41571-019-0218-0Martins F., Sofiya L., Sykiotis G.P., et al. Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat Rev Clin Oncol 2019;16(9):563–580. https://doi.org/10.1038/S41571-019-0218-0Salam S., Lavin T., Turan A. Limbic encephalitis following immunotherapy against metastatic malignant melanoma. BMJ Case Rep 2016;2016:bcr2016215012. https://doi.org/10.1136/bcr-2016-215012Salam S., Lavin T., Turan A. Limbic encephalitis following immunotherapy against metastatic malignant melanoma. BMJ Case Rep 2016;2016:bcr2016215012. https://doi.org/10.1136/bcr-2016-215012Thompson J.A., Schneider B.J., Brahmer J., et al. Management of Immunotherapy-Related Toxicities, Version 1.2019. J Natl Compr Canc Netw 2019;17(3):255–289. https://doi.org/10.6004/jnccn.2019.0013Thompson J.A., Schneider B.J., Brahmer J., et al. Management of Immunotherapy-Related Toxicities, Version 1.2019. J Natl Compr Canc Netw 2019;17(3):255–289. https://doi.org/10.6004/jnccn.2019.0013Xu M., Nie Y., Yang Y., et al. Risk of Neurological Toxicities Following the Use of Different Immune Checkpoint Inhibitor Regimens in Solid Tumors: A Systematic Review and Meta-analysis. Neurologist 2019;24(3):75–83. https://doi.org/10.1097/NRL.0000000000000230Xu M., Nie Y., Yang Y., et al. Risk of Neurological Toxicities Following the Use of Different Immune Checkpoint Inhibitor Regimens in Solid Tumors: A Systematic Review and Meta-analysis. Neurologist 2019;24(3):75–83. https://doi.org/10.1097/NRL.0000000000000230Li Y., Zhang X., Zhao C. Guillain-Barré Syndrome-Like Polyneuropathy Associated with Immune Checkpoint Inhibitors: A Systematic Review of 33 Cases. Biomed Res Int 2021;2021:9800488. https://doi.org/10.1155/2021/9800488Li Y., Zhang X., Zhao C. Guillain-Barré Syndrome-Like Polyneuropathy Associated with Immune Checkpoint Inhibitors: A Systematic Review of 33 Cases. Biomed Res Int 2021;2021:9800488. https://doi.org/10.1155/2021/9800488Abdel-Rahman O., Oweira H., Petrausch U., et al. Immune-related ocular toxicities in solid tumor patients treated with immune checkpoint inhibitors: a systematic review. Expert Rev Anticancer Ther 2017;17(4):387–394. https://doi.org/10.1080/14737140.2017.1296765Abdel-Rahman O., Oweira H., Petrausch U., et al. Immune-related ocular toxicities in solid tumor patients treated with immune checkpoint inhibitors: a systematic review. Expert Rev Anticancer Ther 2017;17(4):387–394. https://doi.org/10.1080/14737140.2017.1296765Anquetil C., Salem J.E., Lebrun-Vignes B., et al. Evolving spectrum of drug-induced uveitis at the era of immune checkpoint inhibitors results from the WHO’s pharmacovigilance database. J Autoimmun 2020;111:102454. https://doi.org/10.1016/j.jaut.2020.102454Anquetil C., Salem J.E., Lebrun-Vignes B., et al. Evolving spectrum of drug-induced uveitis at the era of immune checkpoint inhibitors results from the WHO’s pharmacovigilance database. J Autoimmun 2020;111:102454. https://doi.org/10.1016/j.jaut.2020.102454Bomze D., Meirson T., Hasan Ali O., et al. Ocular Adverse Events Induced by Immune Checkpoint Inhibitors: A Comprehensive Pharmacovigilance Analysis. Ocul Immunol Inflamm 2022;30(1):191–197. https://doi.org/10.1080/09273948.2020.1773867Bomze D., Meirson T., Hasan Ali O., et al. Ocular Adverse Events Induced by Immune Checkpoint Inhibitors: A Comprehensive Pharmacovigilance Analysis. Ocul Immunol Inflamm 2022;30(1):191–197. https://doi.org/10.1080/09273948.2020.1773867Nguyen A.T., Elia M., Materin M.A., et al. Cyclosporine for Dry Eye Associated With Nivolumab: A Case Progressing to Corneal Perforation. Cornea 2016;35(3):399–401. https://doi.org/10.1097/ICO.0000000000000724Nguyen A.T., Elia M., Materin M.A., et al. Cyclosporine for Dry Eye Associated With Nivolumab: A Case Progressing to Corneal Perforation. Cornea 2016;35(3):399–401. https://doi.org/10.1097/ICO.0000000000000724Hahn L., Pepple K.L. Bilateral neuroretinitis and anterior uveitis following ipilimumab treatment for metastatic melanoma. J Ophthalmic Inflamm Infect 2016;6:14. https://doi.org/10.1186/S12348-016-0082-3Hahn L., Pepple K.L. Bilateral neuroretinitis and anterior uveitis following ipilimumab treatment for metastatic melanoma. J Ophthalmic Inflamm Infect 2016;6:14. https://doi.org/10.1186/S12348-016-0082-3Wilson M.A., Guld K., Galetta S., et al. Acute visual loss after ipilimumab treatment for metastatic melanoma. J Immunother Cancer 2016;4:66. https://doi.org/10.1186/S40425-016-0170-9Wilson M.A., Guld K., Galetta S., et al. Acute visual loss after ipilimumab treatment for metastatic melanoma. J Immunother Cancer 2016;4:66. https://doi.org/10.1186/S40425-016-0170-9Zhang H., Houadj L., Wu K.Y., Tran S.D. Diagnosing and Managing Uveitis Associated with Immune Checkpoint Inhibitors: A Review. Diagnostics (Basel) 2024;14(3):336. https://doi.org/10.3390/diagnostics14030336Zhang H., Houadj L., Wu K.Y., Tran S.D. Diagnosing and Managing Uveitis Associated with Immune Checkpoint Inhibitors: A Review. Diagnostics (Basel) 2024;14(3):336. https://doi.org/10.3390/diagnostics14030336Bloch-Michel E., Nussenblatt R.B. International Uveitis Study Group recommendations for the evaluation of intraocular inflammatory disease. Am J Ophthalmol 1987;103(2):234–235. https://doi.org/10.1016/S0002-9394(14)74235-7Bloch-Michel E., Nussenblatt R.B. International Uveitis Study Group recommendations for the evaluation of intraocular inflammatory disease. Am J Ophthalmol 1987;103(2):234–235. https://doi.org/10.1016/S0002-9394(14)74235-7Chang C.J., Chen S.J., Hwang D.K., Liu C. Bilateral anterior uveitis after immunotherapy for malignant melanoma. Taiwan J Ophthalmol 2018;8(3):173–175. https://doi.org/10.4103/tjo.tjo_88_17.Chang C.J., Chen S.J., Hwang D.K., Liu C. Bilateral anterior uveitis after immunotherapy for malignant melanoma. Taiwan J Ophthalmol 2018;8(3):173–175. https://doi.org/10.4103/tjo.tjo_88_17.Deschenes J., Murray P.I., Rao N.A., Nussenblatt R.B. International Uveitis Study Group (IUSG): clinical classification of uveitis. Ocul Immunol Inflamm 2008;16(1):1–2. https://doi.org/10.1080/09273940801899822Deschenes J., Murray P.I., Rao N.A., Nussenblatt R.B. International Uveitis Study Group (IUSG): clinical classification of uveitis. Ocul Immunol Inflamm 2008;16(1):1–2. https://doi.org/10.1080/09273940801899822Sun M.M., Kelly S.P., Mylavarapu BS A.L., et al. Ophthalmic Immune-Related Adverse Events after Anti-CTLA-4 or PD-1 Therapy Recorded in the American Academy of Ophthalmology Intelligent Research in Sight Registry. Ophthalmology 2021;128(6):910–919. https://doi.org/10.1016/J.ophtha.2020.11.001Sun M.M., Kelly S.P., Mylavarapu BS A.L., et al. Ophthalmic Immune-Related Adverse Events after Anti-CTLA-4 or PD-1 Therapy Recorded in the American Academy of Ophthalmology Intelligent Research in Sight Registry. Ophthalmology 2021;128(6):910–919. https://doi.org/10.1016/J.ophtha.2020.11.001Braun D., Getahun D., Chiu V.Y., et al. Population-Based Frequency of Ophthalmic Adverse Events in Melanoma, Other Cancers, and After Immune Checkpoint Inhibitor Treatment. Am J Ophthalmol 2021;224:282–291. https://doi.org/10.1016/J.AJO.2020.12.013Braun D., Getahun D., Chiu V.Y., et al. Population-Based Frequency of Ophthalmic Adverse Events in Melanoma, Other Cancers, and After Immune Checkpoint Inhibitor Treatment. Am J Ophthalmol 2021;224:282–291. https://doi.org/10.1016/J.AJO.2020.12.013Zhou L., Wei X. Ocular Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors in Lung Cancer. Front Immunol 2021;12:701951. https://doi.org/10.3389/FIMMU.2021.701951Zhou L., Wei X. Ocular Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors in Lung Cancer. Front Immunol 2021;12:701951. https://doi.org/10.3389/FIMMU.2021.701951Guex-Crosier Y. Do Naranjo Criteria Still Apply to Ipilimumab-induced Uveitis? Klin Monbl Augenheilkd 2016;233(4):356. https://doi.org/10.1055/S-0042-104249Guex-Crosier Y. Do Naranjo Criteria Still Apply to Ipilimumab-induced Uveitis? Klin Monbl Augenheilkd 2016;233(4):356. https://doi.org/10.1055/S-0042-104249Naranjo C.A., Busto U., Sellers E.M., et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30(2):239–245. https://doi.org/10.1038/CLPT.1981.154Naranjo C.A., Busto U., Sellers E.M., et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30(2):239–245. https://doi.org/10.1038/CLPT.1981.154Boyd S.R., Young S., Lightman S. Immunopathology of the noninfectious posterior and intermediate uveitides. Surv Ophthalmol 2001;46(3):209–233. https://doi.org/10.1016/S0039-6257(01)00275-2Boyd S.R., Young S., Lightman S. Immunopathology of the noninfectious posterior and intermediate uveitides. Surv Ophthalmol 2001;46(3):209–233. https://doi.org/10.1016/S0039-6257(01)00275-2Pasadhika S., Rosenbaum J.T. Ocular Sarcoidosis. Clin Chest Med 2015;36(4):669–683. https://doi.org/10.1016/J.CCM.2015.08.009Pasadhika S., Rosenbaum J.T. Ocular Sarcoidosis. Clin Chest Med 2015;36(4):669–683. https://doi.org/10.1016/J.CCM.2015.08.009Regatieri C.V., Alwassia A., Zhang J.Y., et al. Use of optical coherence tomography in the diagnosis and management of uveitis. Int Ophthalmol Clin 2012;52(4):33–43. https://doi.org/10.1097/IIO.0B013E318265D439Regatieri C.V., Alwassia A., Zhang J.Y., et al. Use of optical coherence tomography in the diagnosis and management of uveitis. Int Ophthalmol Clin 2012;52(4):33–43. https://doi.org/10.1097/IIO.0B013E318265D439Parikh R.A., Chaon B.C., Berkenstock M.K. Ocular Complications of Checkpoint Inhibitors and Immunotherapeutic Agents: A Case Series. Ocul Immunol Inflamm 2021;29(7–8):1585–1590. https://doi.org/10.1080/09273948.2020.1766082Parikh R.A., Chaon B.C., Berkenstock M.K. Ocular Complications of Checkpoint Inhibitors and Immunotherapeutic Agents: A Case Series. Ocul Immunol Inflamm 2021;29(7–8):1585–1590. https://doi.org/10.1080/09273948.2020.1766082Mazharuddin A.A., Whyte A.T., Gombos D.S., et al. Highlights on Ocular Toxicity of Immune Checkpoint Inhibitors at a US Tertiary Cancer Center. J Immunother Precis Oncol 2022;5(4):98–104. https://doi.org/10.36401/JIPO-22-14Mazharuddin A.A., Whyte A.T., Gombos D.S., et al. Highlights on Ocular Toxicity of Immune Checkpoint Inhibitors at a US Tertiary Cancer Center. J Immunother Precis Oncol 2022;5(4):98–104. https://doi.org/10.36401/JIPO-22-14Martens A., Schauwvlieghe P.P., Madoe A., et al. Ocular adverse events associated with immune checkpoint inhibitors, a scoping review. J Ophthalmic Inflamm Infect 2023;13(1):5. https://doi.org/10.1186/S12348-022-00321-2Martens A., Schauwvlieghe P.P., Madoe A., et al. Ocular adverse events associated with immune checkpoint inhibitors, a scoping review. J Ophthalmic Inflamm Infect 2023;13(1):5. https://doi.org/10.1186/S12348-022-00321-2Dick A.D., Rosenbaum J.T., Al-Dhibi H.A., et al. Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative. Ophthalmology 2018;125(5):757–773. https://doi.org/10.1016/j.ophtha.2017.11.017Dick A.D., Rosenbaum J.T., Al-Dhibi H.A., et al. Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative. Ophthalmology 2018;125(5):757–773. https://doi.org/10.1016/j.ophtha.2017.11.017Karim R., Sykakis E., Lightman S., Fraser-Bell S. Interventions for the treatment of uveitic macular edema: a systematic review and meta-analysis. Clin Ophthalmol 2013;7:1109–1144. https://doi.org/10.2147/OPTH.S40268Karim R., Sykakis E., Lightman S., Fraser-Bell S. Interventions for the treatment of uveitic macular edema: a systematic review and meta-analysis. Clin Ophthalmol 2013;7:1109–1144. https://doi.org/10.2147/OPTH.S40268Heiligenhaus A., Minden K., Tappeiner C., et al. Update of the evidence based, interdisciplinary guideline for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis. Semin Arthritis Rheum 2019;49(1):43–55. https://doi.org/10.1016/j.semarthrit.2018.11.004Heiligenhaus A., Minden K., Tappeiner C., et al. Update of the evidence based, interdisciplinary guideline for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis. Semin Arthritis Rheum 2019;49(1):43–55. https://doi.org/10.1016/j.semarthrit.2018.11.004De Filette J.M.K., Pen J.J., Decoster L., et al. Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review. Eur J Endocrinol 2019;181(3):363–374. https://doi.org/10.1530/EJE-19-0291De Filette J.M.K., Pen J.J., Decoster L., et al. Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review. Eur J Endocrinol 2019;181(3):363–374. https://doi.org/10.1530/EJE-19-0291Mellati M., Eaton K.D., Brooks-Worrell B.M., et al. Anti-PD-1 and Anti-PDL-1 Monoclonal Antibodies Causing Type 1 Diabetes. Diabetes Care 2015;38(9):e137–138. https://doi.org/10.2337/DC15-0889Mellati M., Eaton K.D., Brooks-Worrell B.M., et al. Anti-PD-1 and Anti-PDL-1 Monoclonal Antibodies Causing Type 1 Diabetes. Diabetes Care 2015;38(9):e137–138. https://doi.org/10.2337/DC15-0889Godwin J.L., Jaggi S., Sirisena I., et al. Nivolumab-induced autoimmune diabetes mellitus presenting as diabetic ketoacidosis in a patient with metastatic lung cancer. J Immunother Cancer 2017;5:40. https://doi.org/10.1186/S40425-017-0245-2Godwin J.L., Jaggi S., Sirisena I., et al. Nivolumab-induced autoimmune diabetes mellitus presenting as diabetic ketoacidosis in a patient with metastatic lung cancer. J Immunother Cancer 2017;5:40. https://doi.org/10.1186/S40425-017-0245-2Delanoy N., Michot J.M., Comont T., et al. Haematological immune-related adverse events induced by anti-PD-1 or anti-PD-L1 immunotherapy: a descriptive observational study. Lancet Haematol 2019;6(1):e48-е57. https://doi.org/10.1016/S2352-3026(18)30175-3Delanoy N., Michot J.M., Comont T., et al. Haematological immune-related adverse events induced by anti-PD-1 or anti-PD-L1 immunotherapy: a descriptive observational study. Lancet Haematol 2019;6(1):e48-е57. https://doi.org/10.1016/S2352-3026(18)30175-3Michot J.M., Lazarovici J., Tieu A., et al. Haematological immune-related adverse events with immune checkpoint inhibitors, how to manage? Eur J Cancer 2019;122:72–90. https://doi.org/10.1016/J.EJCA.2019.07.014Michot J.M., Lazarovici J., Tieu A., et al. Haematological immune-related adverse events with immune checkpoint inhibitors, how to manage? Eur J Cancer 2019;122:72–90. https://doi.org/10.1016/J.EJCA.2019.07.014Mullally W.J., Cooke F.J., Crosbie I.M., et al. Case Report: Thrombotic-Thrombocytopenic Purpura Following Ipilimumab and Nivolumab Combination Immunotherapy for Metastatic Melanoma. Front Immunol 2022;13:871217. https://doi.org/10.3389/FIMMU.2022.871217Mullally W.J., Cooke F.J., Crosbie I.M., et al. Case Report: Thrombotic-Thrombocytopenic Purpura Following Ipilimumab and Nivolumab Combination Immunotherapy for Metastatic Melanoma. Front Immunol 2022;13:871217. https://doi.org/10.3389/FIMMU.2022.871217Zaremba A., Kramer R., De Temple V., et al. Grade 4 Neutropenia Secondary to Immune Checkpoint Inhibition - A Descriptive Observational Retrospective Multicenter Analysis. Front Oncol 2021;11:765608. https://doi.org/10.3389/FONC.2021.765608Zaremba A., Kramer R., De Temple V., et al. Grade 4 Neutropenia Secondary to Immune Checkpoint Inhibition - A Descriptive Observational Retrospective Multicenter Analysis. Front Oncol 2021;11:765608. https://doi.org/10.3389/FONC.2021.765608Kramer R., Zaremba A., Moreira A., Ugurel S., et al. Hematological immune related adverse events after treatment with immune checkpoint inhibitors. Eur J Cancer 2021;147:170–181. https://doi.org/10.1016/J.EJCA.2021.01.013Kramer R., Zaremba A., Moreira A., Ugurel S., et al. Hematological immune related adverse events after treatment with immune checkpoint inhibitors. Eur J Cancer 2021;147:170–181. https://doi.org/10.1016/J.EJCA.2021.01.013Delyon J., Mateus C., Lambert T. Hemophilia A induced by ipilimumab. N Engl J Med 2011;365(18):1747–1748. https://doi.org/10.1056/NEJMC1110923Delyon J., Mateus C., Lambert T. Hemophilia A induced by ipilimumab. N Engl J Med 2011;365(18):1747–1748. https://doi.org/10.1056/NEJMC1110923Noseda R., Bertoli R., Müller L., Ceschi A. Haemophagocytic lymphohistiocytosis in patients treated with immune checkpoint inhibitors: analysis of WHO global database of individual case safety reports. J Immunother Cancer 2019;7(1):117. https://doi.org/10.1186/S40425-019-0598-9Noseda R., Bertoli R., Müller L., Ceschi A. Haemophagocytic lymphohistiocytosis in patients treated with immune checkpoint inhibitors: analysis of WHO global database of individual case safety reports. J Immunother Cancer 2019;7(1):117. https://doi.org/10.1186/S40425-019-0598-9Davis E.J., Salem J.-E., Young A., et al. Hematologic Complications of Immune Checkpoint Inhibitors. Oncologist 2019;24(5):584–588. https://doi.org/10.1634/theoncologist.2018-0574Davis E.J., Salem J.-E., Young A., et al. Hematologic Complications of Immune Checkpoint Inhibitors. Oncologist 2019;24(5):584–588. https://doi.org/10.1634/theoncologist.2018-0574Martin M., Nguyen H.M., Beuvon C., et al. Immune Checkpoint Inhibitor-Related Cytopenias: About 68 Cases from the French Pharmacovigilance Database. Cancers (Basel) 2022;14(20):5030. https://doi.org/10.3390/cancers14205030.Martin M., Nguyen H.M., Beuvon C., et al. Immune Checkpoint Inhibitor-Related Cytopenias: About 68 Cases from the French Pharmacovigilance Database. Cancers (Basel) 2022;14(20):5030. https://doi.org/10.3390/cancers14205030.

The authors declare that there are no conflicts of interest present.