Endocrinopathies Associated with Immune Checkpoint Inhibitors

Authors

  • Irena Druce, MD, MSc, FRCPC Division of Endocrinology, Department of Medicine, University of Ottawa; Chronic Disease Program, The Ottawa Hospital Research Institute

DOI:

https://doi.org/10.58931/cdet.2023.1210

Abstract

Immune checkpoint receptors are expressed by cells of the immune system and lead to reduced or absent function, which physiologically limits autoimmunity. These receptors are also exploited by malignant cells to maintain immune tolerance and evade destruction. Monoclonal antibodies targeting immune checkpoints have revolutionized oncology, with potential long-lasting clinical response, even in the setting of metastatic solid tumors. For example, in the past, metastatic melanoma signalled certain death; now, remission is possible.

The primary targets of current pharmacotherapy are cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and the programmed cell death protein 1 (PD-1) and its ligand (PD-L1). Today, half of all patients with metastatic disease are eligible to receive immune checkpoint inhibitor (ICI) therapy. As of December 2021, there were eight approved agents available for 17 malignancies, and more than 1,000 clinical trials have been conducted to explore these agents in adjuvant and maintenance settings.

The immune activation that underlies ICI therapy and the persistence of clinical response beyond the pharmacologic half-life also explain the toxicities that have been observed. Immune-related adverse events (irAEs) from ICI therapy have been shown to occur in virtually every organ system. They manifest at varying times during treatment, sometimes occurring after its discontinuation. Interestingly, the presence of these adverse events (AEs) is related to the immune system’s degree of self-tolerance and predicts patient response to this treatment modality.

Endocrinopathies are some of the most common irAEs, occurring in 15–40% of patients; however, they have posed challenges for clinicians as they are difficult to diagnose due to diverse and non-specific manifestations. In contrast to other irAEs, endocrinopathies do not respond to high-dose glucocorticoids and they are permanent. Steroid treatment has been shown to have no effect on the disease severity or the likelihood of resolution. Fortunately, when diagnosed appropriately, ICI-associated endocrinopathies are easy to treat, do not necessitate treatment discontinuation, and have an excellent prognosis.

Author Biography

Irena Druce, MD, MSc, FRCPC, Division of Endocrinology, Department of Medicine, University of Ottawa; Chronic Disease Program, The Ottawa Hospital Research Institute

Dr. Irena Druce completed her studies, including a Masters’ in Cellular and Molecular Medicine and her medical education, at the University of Ottawa. She practices in the community and as a part-time associate with The Ottawa Hospital. She is an assistant professor with the Department of Medicine at the University of Ottawa and has collaborated with medical oncology on research into endocrine side effects of immune checkpoint inhibitor therapy. Her other clinical interests include type 2 diabetes and transgender medicine.

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Published

2023-06-19

How to Cite

Druce, I. (2023). Endocrinopathies Associated with Immune Checkpoint Inhibitors. Canadian Diabetes & Endocrinology Today, 1(2), 5–8. https://doi.org/10.58931/cdet.2023.1210

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Articles