Immune-Mediated Adverse  Events Associated With Immune Checkpoint  Inhibitors Therapy

Реутова, Е. В.; Лактионов, К. П.; Бредер, В. В.; Саранцева, К. А.; Окружнова, М А; Перегудова, М. В.

doi:10.18027/2224-5057-2016-4-68-76

Cited by 8 publications

(6 citation statements)

References 21 publications

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“…Зуд, значительно снижающий качество жизни пациентов в связи с его высокой устойчивостью к стандартной противозудной терапии, мог сопровождаться сыпью либо развиваться без нее. В научной литературе были описаны и такие редкие виды реакций со стороны кожи, как лихеноидные, буллезные поражения, включая буллезный пемфигоид [74][75][76][77][78].…”

Section: анализ нежелательных реакций связанных с применением ингибиunclassified

“…Данные гистологических Таблица 3. Частота возникновения иммуноопосредованных нежелательных реакций, связанных с применением ингибиторов иммунных контрольных точек [5,7,45,51,[74][75][76][77][78][79][80][81][82][83][84][85][86][87][88] исследований при пневмоните показали картину организующейся пневмонии, поражения альвеол и гранулематозного воспаления с вариабельным соотношением CD4 и CD8 лимфоцитов в инфильтрате [97,101]. Анализ проведенных исследований позволил выявить, что частота пневмонита на фоне терапии ингибиторами ИКТ была выше у пациентов с НМРЛ и метастатическим почечноклеточным раком, чем у пациентов с меланомой [100,101].…”

Section: анализ нежелательных реакций связанных с применением ингибиunclassified

“…Incidence of immune-mediated adverse reactions associated with the use of immune checkpoint inhibitors[5,7,45,51,[74][75][76][77][78][79][80][81][82][83][84][85][86][87][88] …”

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Immune Response Checkpoint Inhibitors: New Risks of a New Class of Antitumor Agents

Шубникова¹,

Букатина²,

Вельц³

et al. 2020

Bezopasnost' i risk farmakoterapii

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The introduction into clinical practice of immune checkpoint inhibitors that block cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death ligand-1 (PD-L1), has improved the prognosis of patients with malignant neoplasms of diﬀ erent localisation. The antitumour eﬀ ect of immune checkpoint inhibitors is based on blocking CTLA-4 and PD-1/PD-L1 signaling pathways and enhancing lymphocyte antitumour activity. However, inhibition of immune checkpoints may lead to dysregulation of immune responses and appearance of a new type of adverse reactions resulting from changes in the activity of immunocompetent cells. The aim of the study was to analyse adverse reactions associated with the use of immune checkpoint inhibitors. It was demonstrated that the structure of immune-mediated adverse reactions varied depending on the class of immune checkpoint inhibitors. The incidence of immune-mediated adverse reactions was higher with CTLA-4 inhibitors as compared with PD-1/PD-L1 inhibitors, and increased signiﬁ cantly in the case of combination therapy. The treatment with CTLA-4 inhibitors most often resulted in skin reactions (rash, itching), gastrointestinal tract reactions (diarrhea, colitis), and endocrine gland problems (hypophysitis). The treatment with PD-1 inhibitors most often led to respiratory disorders (pneumonitis), and in some cases to gastrointestinal disorders (diarrhea, colitis), skin reactions (rash, itching), and endocrine gland problems (hypothyroidism), but they were less common. The treatment with PD-L1 inhibitors was associated with the development of pneumonitis. The development of immune-mediated adverse reactions may require discontinuation of treatment and administration of immunosuppressants, therefore early diagnosis and timely treatment of complications are important prerequisites for successful antitumour therapy. Further study of the mechanisms of immune-mediated adverse reaction development will optimise antitumour therapy with immune checkpoint inhibitors.

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Section: анализ нежелательных реакций связанных с применением ингибиunclassified

See 1 more Smart Citation

Immune Response Checkpoint Inhibitors: New Risks of a New Class of Antitumor Agents

Шубникова¹,

Букатина²,

Вельц³

et al. 2020

Bezopasnost' i risk farmakoterapii

View full text Add to dashboard Cite

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“…За последние два десятилетия фармакологические подходы к лечению онкологических заболеваний существенно изменились. Если ранее основной целью терапии было нарушение пролиферации опухолевых клеток, то мишенью современных препаратов являются иммунологические контрольные точки: CTLA-4, PD-1 и PD-L1 [6,7].…”

Section: механизм действия моноклональных антителингибиторов контрольunclassified

Lesions in endocrine glands as a complication of immunotherapy in the practice of oncologist

et al. 2019

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This review describes the lesions of the endocrine system that occur as a result of immunotherapy of cancer. This phenomenon is associated with the inhibition by monoclonal antibodies of checkpoints, which do not allow the immune system to affect tumor cells: CTLA-4, PD-1 and PD-L1. Immunotherapy by this group of drugs allows to increase the life expectancy of patients with cancer, but it also leads to the development of autoimmune endocrinopathies (thyroiditis, adrenalitis, diabetes mellitus, hypophysitis), which often manifest by life-threatening conditions. In view of the above, the necessity to carry out regular monitoring of the function of target organs in patients receiving immunotherapy for malignant tumors is discussed. On the other hand, the phenomenon of developing the autoimmune endocrinopathies during therapy with immunological checkpoints inhibitors is of fundamental interest to endocrinologists. Iatrogenic lesions of the endocrine system are unique models of initiation of immune autoagression. Thus, the development of adrenalitis in patients receiving treatment with a PD-1 inhibitor suggests that the PD-1 is involved in the pathogenesis of autoimmune adrenal insufficiency in patients not receiving treatment with this drug. Thus, clarification of the role of PD-1 in the development of adrenalitis is required. The results of such investigations will allow to identify the risk groups for the development of autoimmune adrenal insufficiency and, accordingly, timely diagnosing it and beginning treatment.

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“…Показано, что гиперэкспрессия PD-L1 в опухоли является одним из ключевых механизмов «уклонения» злокачественных клеток от надзора иммунной системы. Моноклональные антитела анти-PD-1 или к его лиганду анти-PD-L1 блокируют рецепторы или лиганд, что предотвращает ингибирование цитотоксических лимфоцитов и тем самым способствует реализации противоопухолевого иммунитета, улучшая результаты лечения злокачественных опухолей [15].…”

Section: прогнозunclassified

Study of association between molecular marker expression on tumor and immunocompetent cells and sensitivity to adjuvant and neoadjuvant therapy of bladder cancer

et al. 2019

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Use of immunotherapy in treatment of muscle-invasive bladder cancer remains the most promising method in case of impossibility of chemotherapy with cisplatin or progression during cisplatin treatment. This approach is the method of choice and can prolong patient’s life. In particular, use of checkpoint inhibitors allows to obtain effective treatment of bladder cancer. However, to prescribe immunotherapeutic medication, patient must have point of application for these drugs. Individualized approach will allow to increase treatment effectiveness and disease prognosis while maximally improving the quality of life.

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Immune-Mediated Adverse Events Associated With Immune Checkpoint Inhibitors Therapy

Cited by 8 publications

References 21 publications

Immune Response Checkpoint Inhibitors: New Risks of a New Class of Antitumor Agents

Immune Response Checkpoint Inhibitors: New Risks of a New Class of Antitumor Agents

Lesions in endocrine glands as a complication of immunotherapy in the practice of oncologist

Study of association between molecular marker expression on tumor and immunocompetent cells and sensitivity to adjuvant and neoadjuvant therapy of bladder cancer

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