Characterization of the onset of thyroid function (TF) abnormalities in patients receiving immune checkpoint inhibitor (CPI) therapy.

Abstract

e22082 Background: Nivolumab (N), Pembrolizumab (P) and ipilimumab (I) are active cancer therapies, however; endocrinopathies are common immune-related adverse events (irAEs). The estimated incidence of TF abnormalities in patients receiving these agents is 10%. Methods: We performed a retrospective review of cancer patients who received CPI therapy with N, P, or I between July 2012 and November 2016 – for various indications- through our integrated community-based health system. The primary aim was to characterize the onset of TF abnormalities and the potential predictors of their development. Patients with pre-existing TF abnormalities, prior head and neck radiation, or prior thyroid surgery were excluded. TF abnormalities were classified as thyrotoxicosis (defined as low TSH, or an elevation of FT4 or FT3) or hypothyroidism (defined as an elevation in TSH, or a reduced level of FT4 or FT3). Patient demographics, diagnosis, treatment type, associated symptoms, and number of days before detection (NDBD) of TF abnormality were reviewed. Results: Of 361 eligible patients reviewed, 50 patients (13.85%) developed new onset of TF abnormalities. Among those with TF abnormalities, the median age at the time of receiving immunotherapy was 64. 29 patients (58%) received N, 12 received P (24%), 4 patients received I (8%), and 5 patients received N + I (10%). Thyrotoxicosis was the most commonly noted initial abnormality (n = 27, 54%), compared to hypothyroidism (n = 23,46%). Only 58% of patients had clinically evident symptoms. No significant difference was found between the mean of NDBD of TF abnormality between hypothyroidism and thyrotoxicosis (89 versus 78 days, P = 0.57). The time frame for TF abnormality detection was not significantly different between males and females receiving CPI therapy (71 versus 97 days, P = 0.17). Conclusions: The incidence of CPI related TF abnormalities at our center is similar to clinical trial findings. CPI therapy is associated with different patterns of TF abnormalities. The majority of patients who developed laboratory evidence of abnormal thyroid function were asymptomatic. Ongoing research is exploring the impact of these irAE on patient outcome.