Endocrine adverse events of immune checkpoint inhibitors: results of a single-center study

Abstract

Immune checkpoint inhibitors (ICPIs) agents can cause endocrine immune-related adverse events (irAEs).Aim. Determine the incidence, time of onset and risk factors of endocrine irAEs in cancer patients treated with anti-PD1 and anti-CTLA-4 immunotherapy.Materials and methods. This is a retrospective single-center study that included 61 patients aged 28 to 81 years with diagnosed cancer of the lungs, ovaries, esophagus, stomach, bladder, kidney, and pleural mesothelioma. 44 (72%) patients received anti-PDL1/anti-PD1 monotherapy and 17 (28%) received a combination of anti-PD1 + anti-CTLA-4. Calculated: odds ratio (OR) and 95% confidence interval (CI).Results. The incidence of endocrine irAEs was 23% (14 patients): thyroiditis (13%), hypophysitis (8%), adrenal insufficiency and diabetes mellitus (2–3%). IrAEs occurred in 9 (20%) patients with monotherapy and in 5 (35%) patients when using a combination of drugs (p=0.318). The average time of onset of irAEs did not differ depending on the applied regimen and amounted to 6 [4–18] weeks. Symptomatic irAEs developed in 2 (13%) patients. Discontinuation of ICPI therapy due to irAE was not required in any case. Risk factors: age younger than 61 years old – OR 4.4 (95% CI 1.198–16.242), female OR 2.4 (95% CI 0.67–8.591), presence of stage IV disease – OR 2.4 (95% CI 0.689–8.362), combination therapy OR 1.855 (95% CI 0.548–6.277), previous endocrine pathology – OR 0.813 (95% CI 0.152–4.356).Conclusions. The incidence of endocrine irAEs when using ICPI is 23%. Thyroiditis and hypophysitis develop more often. The odds are higher in patients younger than 61 years. In most cases, irAEs are not symptomatic and do not require discontinuation of ICPI therapy.

Keywords

• immune checkpoint inhibitors
• hypophysitis
• thyroiditis
• adrenal insufficiency
• diabetes mellitus
• adverse effects