medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2022-16-9-22-28medsovet-6911Research ArticleИММУНОТЕРАПИЯ ОПУХОЛЕЙIMMUNOTHERAPY IN ONCOLOGYКлючевые внутриклассовые отличия ингибиторов PD-1/PD-L1Key differences between anti-PD-1/PD-L1 inhibitorshttps://orcid.org/0000-0002-0619-2205ЖуковаН. В.ZhukovaN. V.

Жукова Наталья Владимировна – кандидат медицинских наук, доцент кафедры онкологии, СПбГУ; врач-онколог, заведующая химиотерапевтическим отделением (противоопухолевой лекарственной терапии) №13, ГКОД.

199034, Санкт-Петербург, Университетская наб., д. 7-9; 198255, Санкт-Петербург, пр-т Ветеранов, д. 56.

Natalia V. Zhukova - Cand. Sci. (Med.), Associate Professor, Department of Oncology, St Petersburg State University; Oncologist, Head of Chemotherapy Department (Antineoplastic Drug Therapy) No. 13, City Clinical Oncology Center.

7-9, Universitetskaya Emb., St Petersburg, 199034; 56, Veteranov Ave., St Petersburg, 198255.

drnvz@yandex.ruhttps://orcid.org/0000-0003-4447-9458ОрловаР. В.OrlovaR. V.

Орлова Рашида Вахидовна – доктор медицинских наук, профессор, заведующая кафедрой онкологии СПбГУ; врач-онколог, главный специалист по клинической онкологии, ГКОД.

199034, Санкт-Петербург, Университетская наб., д. 7-9; 198255, Санкт-Петербург, пр-т Ветеранов, д. 56.

Rashida V. Orlova - Dr. Sci. (Med.), Professor, Head of the Department of Oncology, St Petersburg State University; Oncologist, Chief Specialist in Clinical Oncology, City Clinical Oncology Center.

7-9, Universitetskaya Emb., St Petersburg, 199034; 56, Veteranov Ave., Saint Petersburg, 198255.

orlova_rashida@mail.ruhttps://orcid.org/0000-0002-9628-7098КалединаЕ. А.KaledinaE. A.

Каледина Екатерина Александровна - врач-онколог отделения противоопухолевой лекарственной терапии №10.

198255, Санкт-Петербург, пр-т Ветеранов, д. 56.

Ekaterina A. Kaledina - Oncologist, Department of Antitumor Drug Therapy No. 10, City Clinical Oncology Center.

56, Veteranov Ave., St Petersburg, 198255.

kate199595@mail.ruhttps://orcid.org/0000-0003-1830-9287НаймушинаП. A.NaymushinaP. A.

Наймушина Полина Андреевна - студентка 5-го курса медицинского факультета.

199034, Санкт-Петербург, Университетская наб., д. 7-9.

Polina A. Naymushina - 5th Year Student of the Faculty of Medicine, St Petersburg State University.

7-9, Universitetskaya Emb., St Petersburg, 199034.

polina.naymushina1@gmail.comhttps://orcid.org/0000-0002-6008-1354МалковаА. М.MalkovaA. M.

Малкова Анна Михайловна - аспирант кафедры онкологии, младший научный сотрудник лаборатории мозаики аутоиммунитета, СПбГУ; младший научный сотрудник лаборатории биомедицинского материаловедения, ПСПбГМУ им. ак. И.П. Павлова.

199034, Санкт-Петербург, Университетская наб., д. 7-9; 197022, Санкт-Петербург, ул. Льва Толстого, д. 6-8.

Anna M. Malkova - Postgraduate Student of the Department of Oncology, Junior Researcher, Laboratory of Autoimmunity Mosaic, St Petersburg State University; Junior Researcher, Laboratory of Biomedical Materials Science, Pavlov First Saint Petersburg State Medical University.

7-9, Universitetskaya Emb., St Petersburg, 199034; 6-8, Lev Tolstoy St., St Petersburg, 197022.

anya.malkova.95@mail.ruhttps://orcid.org/0000-0003-0402-6067БелякН. П.BeliakN. P.

Беляк Наталья Петровна – кандидат медицинских наук, ассистент кафедры онкологии, СПбГУ; врач-онколог, заведующая отделением противоопухолевой лекарственной терапии №10, ГКОД.

199034, Санкт-Петербург, Университетская наб., д. 7-9; 198255, Санкт-Петербург, пр-т Ветеранов, д. 56.

Natalia P. Beliak - Cand. Sci. (Med.), Assistant of the Department of Oncology, St Petersburg State University; Oncologist, Head of the Department of Antitumor Drug Therapy No. 10, City Clinical Oncology Center.

7-9, Universitetskaya Emb., St Petersburg, 199034; 56, Veteranov Ave., St Petersburg, 198255.

drnpb@mail.ruСанкт-Петербургский государственный университет; Городской клинический онкологический диспансерРоссияSt Petersburg State University; City Clinical Oncology CenterRussian FederationГородской клинический онкологический диспансерРоссияCity Clinical Oncology CenterRussian FederationСанкт-Петербургский государственный университетРоссияSt Petersburg State UniversityRussian FederationСанкт-Петербургский государственный университет; Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. ПавловаРоссияSt Petersburg State University; Pavlov First Saint Petersburg State Medical UniversityRussian Federation202218062022092228Copyright © Жукова Н.В., Орлова Р.В., Каледина Е.А., Наймушина П.A., Малкова А.М., Беляк Н.П., 20222022Жукова Н.В., Орлова Р.В., Каледина Е.А., Наймушина П.A., Малкова А.М., Беляк Н.П.Zhukova N.V., Orlova R.V., Kaledina E.A., Naymushina P.A., Malkova A.M., Beliak N.P.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/6911

Показания к  назначению иммунотерапии при онкологических заболеваниях продолжают расширяться, в связи с чем возникает все больше вопросов  относительно клинических  аспектов применения различных чекпоинт-ингибиторов. Несмотря на схожий механизм действия активно использующихся    в настоящее время   антител к PD-1 (ниволумаб, пембролизумаб,  пролголимаб) и  PD-L1 (дурвалумаб,   атезолизумаб, авелумаб),   они   значимо  различаются по  токсичности и эффективности    в  силу  особенностей строения моноклональных    антител, на  основе  которых они  созданы. Например, токсичность, приводящая  к прекращению    лечения, чаще  развивалась на  фоне   терапии анти-PD-L1 препаратами,  чем при  назначении  ингибиторов PD-1. Напротив,   средняя частота  развития    иммуноопосредованных нежелательных явлений любой  степени чаще    встречалась у пациентов, получавших терапию анти-PD-1 препаратами. Выявленные  различия в токсичности анализируемых    групп  препаратов   могут  быть  также   связаны   с  направленностью    действия  молекул. Особенностью   ингибиторов PD-L1 является и  то, что при  использовании   данных   препаратов  чаще   развиваются реакции по  механизму   антителозависимой клеточной цитотоксичности. Тем  не менее  именно  ингибиторы PD-1 показали  статистически  значимое  преимущество   в увеличении  выживаемости   согласно  данным   метаанализа, в котором сравнивались группы  анти-PD-1 и  анти-PD-L1. Помимо  различий   в  эффективности   и   токсичности этих  препаратов,    в  статье также проанализированы  имеющиеся данные    об  особенностях  структуры молекул   препаратов,  в  частности, о  роли   мутации LALA у  PD-1 ингибиторов. Понимание    ключевых   отличительных особенностей ингибиторов  PD-1/PD-L1 в  дальнейшем может  позволить    ответить  на   вопрос   о   взаимозаменяемости   чекпоинт-ингибиторов и   повторном   назначении  после купирования  токсичности 3–4-й степени.

Indications  to immunotherapy in cancer treatment continue to expand, thus there are more and more questions about clinical aspects of using different checkpoint inhibitors. Despite similar mechanism of action between widely used antibodies to PD-1 (nivolumab, pembrolizumab, prolgolimab) and PD-L1 (durvalumab, avelumab, atezolizumab), inhibitors are different due to features of monoclonal antibodies structure they are based on. For instance, toxicity leading to discontinuation of treatment occurs more frequently with anti-PD-L1 drugs than PD-1 inhibitors. On the contrary, the average incidence of any grade IRAEs was higher in patients treated with anti-PD-1 drugs. The revealed differences in the toxicity of the analyzed groups of drugs could be associated with the type of action of the drug. The feature of the PD-L1 inhibitors is more frequent occurrence of antibody-dependent cellular cytotoxicity reactions. However, PD-1 inhibitors  showed a statistically significant survival benefit, according to a meta-analysis comparing anti-PD-1 and anti-PD-L1 groups. Besides data on differences in the efficacy and toxicity profiles of these agents, in this article we also analyze different issues in the structure of drug molecules, in particular, the role of LALA mutation in anti-PD-1 inhibitors. Understanding the key distinctive points of check-point inhibitors  (CPI) in the future may allow  to solve the problem of rechallenge  and reintroduction after management of severe IRAEs.

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