medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2020-9-16-24medsovet-5697Research ArticleИММУНОТЕРАПИЯ В ОНКОЛОГИИImmunotherapy in oncologyИммуноопосредованная эндокринопатия у пациентов на фоне лечения ингибиторами контрольных точекImmuno-related endocrinopathy in patients treated with immune checkpoint inhibitorshttps://orcid.org/0000-0002-0620-2696ЮдинД. И.YudinD. I.

Юдин Денис Иванович, к.м.н., старший научный сотрудник

115478, Москва, Каширское шоссе, д. 24

Denis I. Yudin, Cand. of Sci. (Med), Senior Researcher 

24, Kashirskoye Shosse, Moscow, 115478

yudinden@mail.ruhttps://orcid.org/0000-0003-4469-502XЛактионовК. К.LaktionovK. K.

Лактионов Константин Константинович, д.м.н., профессор кафедры онкологии и лучевой терапии лечебного факультета; заведующий онкологическим отделением лекарственных методов лечения (химиотерапевтическое) №17

115478, Москва, Каширское шоссе, д. 24

117997, Москва, ул. Островитянова, д. 1

Konstantin K. Laktionov, Dr. of Sci. (Med), Professor, Chair for Oncology and X-ray Therapy, General Medicine Faculty; Head of Drug Therapy Department (Chemotherapeutic No. 17)

24, Kashirskoye Shosse, Moscow, 115478

1, Ostrovityanov St., Moscow, 117997

lkoskos@mail.ruhttps://orcid.org/0000-0002-7817-8429СаранцеваК. А.SarantsevaK. A.

Саранцева Ксения Андреевна, к.м.н., врач-онколог

115478, Москва, Каширское шоссе, д. 24

Ksenia A. Sarantseva, Cand. of Sci. (Med), Oncologist

24, Kashirskoye Shosse, Moscow, 115478

sarantsevaka@gmail.comhttps://orcid.org/0000-0002-6830-0064БорисоваО. И.BorisovaO. I.

Борисова Ольга Игоревна, врач-онколог

115478, Москва, Каширское шоссе, д. 24

Olga I. Borisova, Oncologist

24, Kashirskoye Shosse, Moscow, 115478

dr_borisova@mail.ruhttps://orcid.org/0000-0002-6244-4294БредерВ. В.BrederV. V.

Бредер Валерий Владимирович, д.м.н., ведущий научный сотрудник

SPIN: 9846-4360 

115478, Москва, Каширское шоссе, д. 24

Valeriy V. Breder, Dr. of Sci. (Med), Lead Researcher

24, Kashirskoye Shosse, Moscow, 115478

vbreder@yandex.ruhttps://orcid.org/0000-0002-2154-3376РеутоваЕ. В.ReutovaE. V.

Реутова Елена Валерьевна, к.м.н., старший научный сотрудник

115478, Москва, Каширское шоссе, д. 24

Elena V. Reutova, Cand. of Sci. (Med), Senior Researcher

24, Kashirskoye Shosse, Moscow, 115478

evreutova@rambler.ruhttps://orcid.org/0000-0002-7897-3422БелоярцеваМ. Ф.BeloyartsevaM. F.

Белоярцева Мария Феликсовна, врач-эндокринолог

115478, Москва, Каширское шоссе, д. 24

Maria F. Beloyartseva,Endocrinologist

24, Kashirskoye Shosse, Moscow, 115478

mfb1973@gmail.comhttps://orcid.org/0000-0002-4573-8477КрутелеваС. Ю.KrutelevaS. Yu.

Крутелева Светлана Юрьевна, аспирантка, врач-онколог

115478, Москва, Каширское шоссе, д. 24

Svetlana Yu. Kruteleva, Postgraduate Student, Oncologist

24, Kashirskoye Shosse, Moscow, 115478

kruteleva2009@mail.ruhttps://orcid.org/0000-0002-6323-511XДжанянИ. А.DzhanyanI. A.

Джанян Ирина Анатольевна, врач-онколог

115478, Москва, Каширское шоссе, д. 24

Irina A. Dzhanyan, Oncologist

24, Kashirskoye Shosse, Moscow, 115478

i-dzhanyan@mail.ruНациональный медицинский онкологический центр им. Н.Н. БлохинаРоссияN.N. Blokhin National Medical Research Center of OncologyRussian FederationНациональный медицинский онкологический центр им. Н.Н. Блохина; Российский национальный исследовательский медицинский университет им. Н.И. ПироговаРоссияN.N. Blokhin National Medical Research Center of Oncology; Pirogov Russian National Research Medical UniversityRussian Federation202027072020091624Copyright © Юдин Д.И., Лактионов К.К., Саранцева К.А., Борисова О.И., Бредер В.В., Реутова Е.В., Белоярцева М.Ф., Крутелева С.Ю., Джанян И.А., 20202020Юдин Д.И., Лактионов К.К., Саранцева К.А., Борисова О.И., Бредер В.В., Реутова Е.В., Белоярцева М.Ф., Крутелева С.Ю., Джанян И.А.Yudin D.I., Laktionov K.K., Sarantseva K.A., Borisova O.I., Breder V.V., Reutova E.V., Beloyartseva M.F., Kruteleva S.Y., Dzhanyan I.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/5697

В последнее время ингибиторы иммунных контрольных точек существенно изменили возможности терапии рака во всем мире. Постоянно увеличивается количество препаратов этой группы и показаний к их применению. В настоящий момент в Российской Федерации зарегистрированы и используется целый ряд ингибиторов иммунных контрольных точек: анти-PD1 (ниволумаб, пембролизумаб), анти-PD-L1 (атезолизумаб, дурвалумаб), анти-CTLA-4-моноклональные антитела (ипилимумаб). Одним из наиболее распространенных осложнений иммунотерапии является иммуноопосредованная эндокринопатия. По данным клинических исследований частота развития серьезных эндокринных иммуноопосредованных нежелательных явлений в целом при монотерапии анти-PD1-моноклональными антителами невелика и составляет 3,5–8%. Однако применение анти-CTLA4-препаратов, комбинированных режимов, проведение иммунотерапии после химиолучевой терапии значительно повышают частоту развития серьезных нежелательных явлений до 30%. В реальной клинической практике иммуноопосредованная эндокринопатия была выявлена у 22 из 245 пациентов (8,9%), получавших иммунотерапию в химиотерапевтическом отделении №17 НМИЦ онкологии им. Н.Н. Блохина по поводу немелкоклеточного рака легкого и гепатоцеллюлярного рака. У большинства пациентов развились нежелательные явления 1–2-й степени, у двух – 3-й степени, что потребовало прекращения лечения. Данная статья имеет своей целью предоставить полезную информацию и дать рекомендации практическим онкологам относительно коррекции часто встречающихся вариантов иммуноопосредованной эндокринопатии (в том числе гипотиреоза, гипертиреоза, гипофизита, надпочечниковой недостаточности).

Recently immune checkpoint inhibitors amazingly changed the landscape of cancer therapy worldwide. The number of immune checkpoint molecules in clinical practice is constantly increasing. There are some monoclonal antibodies recently registered in the Russian Federation: anti-PD1 antibodies (nivolumab, pembrolizumab), anti-PD-L1 (atezolizumab, durvalumab), anti-CTLA-4 (ipilimumab). Immune-mediated endocrinopathies are some of the most common complications of immunotherapy. According to the results of clinical studies, the incidence of serious endocrine immuno-mediated adverse events with anti-PD1 monoclonal antibodies is low (3.5–8%). The use of anti-CTLA4 antibodies, combined regimens, and the use of immunotherapy after chemoradiotherapy significantly increase the incidence of serious adverse events to 30%. In clinical practice of N.N. Blokhin Cancer Research Center among 245 non-small cell lung cancer and hepatocellular carcinoma patients treated with immunotherapy, 22 (8,9%) developed an immune-mediated endocrinopathy. Most patients developed adverse events of 1–2 degrees, in two patients – 3 degrees, requiring discontinuation of treatment. The aim of this article was to provide useful information and recommendations regarding the management of common immuno-related endocrine adverse events (including hypothyroidism, hyperthyroidism, pituitary, adrenal insufficiency) for clinical oncologists.

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