MON-LB007 Incidence and Characteristics of Thyroid and Pituitary Dysfunction in Patients Treated with Immunotherapy

Abstract

Background Endocrinopathies are well recognised immune-related adverse events associated with immunotherapy. Incidence rates of hypophysitis and thyroid dysfunction are widely variable in the literature. Hypophysitis has been reported in between 0.4% and 27% in patients treated with CTLA-4 inhibitors such as ipilimumab (1) while the incidence of thyroid dysfunction varies between 8% and 20% in patients treated with PD-1 inhibitors such as nivolumab and pembrolizumab (1). Aims Our aim was to determine real world rates of thyroid and pituitary dysfunction in patients treated with immunotherapy. We also sought to evaluate the characteristics of same-e.g. time to onset of adverse events and presence of autoantibodies. Methods A retrospective cohort study was performed in 347 patients who received treatment with PD-1 inhibitors nivolumab and pembrolizumab, anti-CD52 antibody alemtuzumab and CTLA-4 inhibitor ipilimumab between January 2013 and December 2017 at a tertiary referral metropolitan hospital in Melbourne, Australia. Patients were identified from pharmacy records and assessment of the clinical and biochemical records pertaining to thyroid function (TFT) and serum cortisol was performed. Results 45 patients (12.9%) had evidence of thyroid or pituitary dysfunction from the therapies. 34 of the 267 (12.7%) patients on PD-1 inhibitors developed thyroid dysfunction, 15 (5.6%) of whom had a clear thyroiditis picture-i.e. thyrotoxic phase with subsequent hypothyroidism. 3 of the 34 (8.8%) patients who received CTLA-4 inhibitor ipilimumab developed hypophysitis, all of whom were on combined treatment with a PD-1 inhibitor. Median time to onset of adverse effects was 30days. 12 out of 27 patients with thyroid dysfunction had positive anti-thyroid peroxidase antibodies. 25 of the 45 (55.6%) patients were reviewed in endocrine outpatient clinics. Only 2 of the 45 endocrinopathies were recorded in the hospital’s adverse drug reactions database. Conclusions In our tertiary centre, endocrinopathies are common in patients treated with immunotherapies; however reportage to the adverse drug reaction database is low and endocrinology services appear underutilised. Current guidelines suggest TFT monitoring every 4-6weeks on therapy (2) with baseline monitoring of early morning ACTH and cortisol concentrations to be considered in patients treated with CTLA-4 inhibitors. Greater clinician awareness and adherence to guidelines is needed for optimal patient care.