Immuno-related endocrinopathy in patients treated with immune checkpoint inhibitors

Abstract

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.

Development of destructive thyroiditis and diabetes mellitus after three injections of pembrolizumab for skin melanoma

“…In contrast to thyroid lesions, which can develop with a frequency of up to 50%, the incidence of diabetes mellitus as an irAE is extremely low [ 8 ]. Nevertheless, it should be remembered that it is possible to develop irAE with damage to several endocrine glands at the same time.…”

“…Taking into account the severity of the manifestations of the main oncological disease, the erased clinical picture of irAEs [6, 7], a rapidly progressive course (in contrast to classical autoimmune diseases of the endocrine system) [ 8 ], irreversibility of the lesion [7, 8] and, in some cases of a life-threatening nature (for example, hypophysitis with the development of secondary adrenal insufficiency, myxedema coma, severe thyrotoxicosis, fulminant diabetes mellitus, adrenalitis) [ 6 ], timely detection of endocrine irAEs is necessary. A fully prescribed therapy makes it possible to continue the immunotherapy of ICPI of the underlying disease in full, and also improves the patient’s quality of life [6, 9].…”