sechenovSechenov Medical JournalСеченовский вестник2218-73322658-3348Сеченовский Университет10.47093/22187332.2019.4.4-11sechenov-175Research ArticleONCOLOGYОНКОЛОГИЯEndocrine adverse events of immune checkpoint inhibitors: results of a single-center studyЭндокринологические осложнения ингибиторов контрольных точек иммунитета: результаты одноцентрового исследованияhttps://orcid.org/0000-0001-6476-6337ПоддубскаяЕ. В.PoddubskayaE. V.

Поддубская Елена Владимировна, канд. мед. наук, заместитель директора Клинического центра по онкологии

г. Москва

Elena V. Poddubskaya, PhD, Deputy Director of Clinical Center for Oncology

Moscow

https://orcid.org/0000-0003-0015-7094СекачеваМ. И.SekachevaM. I.

Секачева Марина Игоревна, д-р мед. наук, профессор, директор института персонализированной медицины, руководитель Центра персонализированной онкологии

г. Москва

Marina I. Sekacheva, DMSc, Professor, Director of the Institute for Personalized Medicine, Director of the Center for Personalized Oncology Sechenov OncoTarget

Moscow

https://orcid.org/0000-0002-6589-2164ГурьяноваА. А.GuryanovaA. A.

Гурьянова Анастасия Андреевна, студентка V курса Международной школы "Медицина будущего" Научно-технологического парк биомедицины

ул. Трубецкая, д. 8, стр. 2, г. Москва, 119991Тел.: +7 (927) 173-00-35 

Anastasia A. Guryanova, 5th year student of the International School "Medicine of the Future" of Biomedical Science & Technology Park

8/2 Trubetskaya st., Moscow, 119991Tel.: +7 (927) 173-00-35 

nt301@yandex.ruФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет)РоссияSechenov First Moscow State Medical University (Sechenov University)Russian Federation201930122019104411Copyright © Poddubskaya E.V., Sekacheva M.I., Guryanova A.A., 20192019Поддубская Е.В., Секачева М.И., Гурьянова А.А.Poddubskaya E.V., Sekacheva M.I., Guryanova A.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.sechenovmedj.com/jour/article/view/175

Immune checkpoint inhibitors (ICPIs) agents can cause endocrine immune-related adverse events (irAEs).

Aim

Aim. Determine the incidence, time of onset and risk factors of endocrine irAEs in cancer patients treated with anti-PD1 and anti-CTLA-4 immunotherapy.

Materials and methods

Materials and methods. This is a retrospective single-center study that included 61 patients aged 28 to 81 years with diagnosed cancer of the lungs, ovaries, esophagus, stomach, bladder, kidney, and pleural mesothelioma. 44 (72%) patients received anti-PDL1/anti-PD1 monotherapy and 17 (28%) received a combination of anti-PD1 + anti-CTLA-4. Calculated: odds ratio (OR) and 95% confidence interval (CI).

Results

Results. The incidence of endocrine irAEs was 23% (14 patients): thyroiditis (13%), hypophysitis (8%), adrenal insufficiency and diabetes mellitus (2–3%). IrAEs occurred in 9 (20%) patients with monotherapy and in 5 (35%) patients when using a combination of drugs (p=0.318). The average time of onset of irAEs did not differ depending on the applied regimen and amounted to 6 [4–18] weeks. Symptomatic irAEs developed in 2 (13%) patients. Discontinuation of ICPI therapy due to irAE was not required in any case. Risk factors: age younger than 61 years old – OR 4.4 (95% CI 1.198–16.242), female OR 2.4 (95% CI 0.67–8.591), presence of stage IV disease – OR 2.4 (95% CI 0.689–8.362), combination therapy OR 1.855 (95% CI 0.548–6.277), previous endocrine pathology – OR 0.813 (95% CI 0.152–4.356).

Conclusions

Conclusions. The incidence of endocrine irAEs when using ICPI is 23%. Thyroiditis and hypophysitis develop more often. The odds are higher in patients younger than 61 years. In most cases, irAEs are not symptomatic and do not require discontinuation of ICPI therapy.

Ингибиторы контрольных точек иммунитета (ИКТИ) могут вызвать иммуноопосредованные нежелательные явления (НЯ) со стороны эндокринной системы.

Цель

Цель. Определить частоту, время развития и факторы риска эндокринологических НЯ при терапии аnti-PD1и anti-CTLA-4-препаратами.

Материалы и методы

Материалы и методы. В ретроспективное одноцентровое исследование включен 61 пациент в возрасте от 28 до 81 года с диагностированным раком легких, яичников, пищевода, желудка, мочевого пузыря, почки и мезотелиомой плевры. Монотерапия anti-PDL1/аnti-PD1 проводилась у 44 (72%), комбинированная (аnti-PD1 + anti-CTLA-4) у 17 (28%) пациентов. Вычислены: отношение шансов (ОШ) и 95% доверительный интервал (ДИ).

Результаты

Результаты. НЯ развились у 14 (23%) пациентов: тиреоидит – у 13%, гипофизит – у 8%, недостаточность надпочечников и сахарный диабет – у 2–3%. При монотерапии НЯ возникли у 9 (20%), при использовании комбинации препаратов – у 5 (35%) пациентов (р=0,318). Среднее время возникновения НЯ от момента начала лечения не отличалось в зависимости от применяемой схемы и составило 6 [4–18] нед. Симптоматические НЯ развились у 2 (13%) пациентов. Приостановка терапии ИКТИ из-за НЯ не потребовалась ни в одном случае. Факторы риска: для возраста моложе 61 года ОШ составило 4,4 (95% ДИ 1,198–16,242), для женского пола ОШ 2,4 (95% ДИ 0,67–8,591), для наличия IV стадии заболевания – ОШ 2,4 (95% ДИ 0,689–8,362), для комбинированной терапии – ОШ 1,855 (95% ДИ 0,548–6,277), для эндокринной патологии в анамнезе – ОШ 0,813 (95% ДИ 0,152–4,356).

Выводы

Выводы. Частота развития эндокринологических НЯ при применении ИКТИ составляет 23%. Чаще развиваются тиреоидит и гипофизит. Шанс НЯ выше у пациентов моложе 61 года. В большинстве случаев НЯ протекают бессимптомно и не требуют отмены терапии ИКТИ.

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