ENDOCRINE TOXICITY OF IMMUNE CHECKPOINT INHIBITORS IN CLINICAL PRACTICE

Abstract

Relevance: Immunological control points significantly changed cancer therapy worldwide after a new class of inhibitor drugs was registered. Based on clinical studies, this type of treatment was associated with better survival in sensitive patients than cytostatic therapy. Checkpoint inhibitors exert their effect by regulating the immune response to malignant cells, blocking the usual inhibitory pathways of T-cell regulation. The receptors of cytotoxic T-lymphocytic antigen-4 (CTLA-4) and programmed cell death protein (PD-1) or its associated ligand (PD-L-1) are the target of inhibitors. CTLA-4 acts at an early stage of triggering an antigenic response, and PD-1 and PD-L-1 act by modulating interaction with peripheral tissue However, treatment with checkpoint inhibitors (ICTs) is accompanied by a wide range of immune mediated adverse events associated with the activation of the immune system. Despite the positive effect on survival, side effects with endocrine effects were noted in about 10% of patients. The study aimed to assess the incidence of immune mediated adverse events from the thyroid gland in clinical practice in patients with different localization of malignant tumors in the first and subsequent lines of therapy with checkpoint inhibitors. Methods: The study utilized anamnestic, laboratory, and instrumental tests. Laboratory analysis included determining the blood levels of TSH, T3, T4, ACTH, and cortisol. Data analysis was carried out using the Microsoft Excel program. Results: The frequency of development of immune mediated thyroiditis against the background of therapy with blockers of control points of the immune pathway in our observation was 29%. The debut of thyroid disorders was diagnosed in the first 12-16 weeks of therapy, beginning with hyperthyroidism against the background of thyroid destruction, followed by a transition to persistent hypothyroidism after 1-3 months. Conclusion: When analyzing the safety profile of ICTs in patients in our study, immune mediated adverse reactions did not differ in frequency and spectrum from world practice. The spectrum of toxicity did not depend on the localization of the tumor. Early diagnosis of thyroid lesions necessary for optimal and effective treatment can be carried out using laboratory tests. Knowing the timing of the development of adverse events during ICT therapy allows timely diagnosing and correcting complications from the thyroid to continue effective therapy.