MON-608 Incidence And Onset Of Thyroid Dysfunction In Patients Treated With Pd-1 Inhibitors At A Medical Center

Background: The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in immune checkpoint therapy for cancer. Pembrolizumab and Nivolumab are anti-PD-1 monoclonal antibodies. Thyroid dysfunction is a known adverse effect of these drugs, but there is limited data on incidence.(1,2) Our aim was to determine the incidence in a consecutive series of patients treated with these drugs. Methods: The study design was a case series. Data from all the patients who received Nivolumab or Pembrolizumab at our Medical Center from July 2016 to July 2018 were reviewed. 123 patients were identified; 21 patients were excluded due to abnormal baseline thyroid function or missing data. 102 patients were included in the study. In addition to descriptive statistics (univariate), bivariate analysis was conducted using the t-test, chi-square, and fisher exact test. Results: The population was male (100%), predominantly white (80%) and elderly (mean age 68.2 + 6.9 years). Indication for treatment was non-small cell lung cancer (NSCLC) in 66.7%. Among the 102 patients, 13 were found to have abnormal thyroid function after medication exposure. 10 of whom developed overt hypothyroidism. Two out of the 10 patients, initially developed thyroiditis, which later progressed to overt hypothyroidism. Three patients developed hyperthyroidism. Onset of thyroid dysfunction was noted within 3.5 doses (range 1-9) and first 7 weeks (range 2-16 weeks) of medication exposure. There were no significant differences between groups regarding age (66.1 vs 68.4 years), race (85 vs 95% white), type of cancer (61.5 vs 68.5% NSCLC), type of drug used (80.9 vs 76.9% Nivolumab) or total number of immunotherapy doses (15.4 vs 10.3) in whom thyroid dysfunction did and did not occur, respectively (all p > 0.2). Discussion: Anti-PD-1 monoclonal antibody-induced thyroid dysfunction is common (12.7%). Yet, there are no standardized protocols of the frequency of thyroid function monitoring in patients treated with these drugs. Interestingly, the onset of thyroid dysfunction occurred on an average within first 7 weeks and 3-4 doses of treatment initiation. Most patients who developed hypothyroidism required long term supplementation. There is no clear association between the number of doses and abnormal thyroid function as previously reported.(1) We suggest that patients that will be started on anti-PD-1 monoclonal antibodies should get thyroid function testing at baseline and monthly for at least the first 2-4 months of treatment, since later the incidence of thyroid abnormalities decreases significantly. References: 1. Yamazaki, H, et al. “Potential Risk Factors for Nivolumab-Induced Thyroid Dysfunction.” In Vivo (Athens, Greece)., U.S. NLM, Nov. 2017. 2. Danae A., et al. “Pembrolizumab-Induced Thyroiditis: Comprehensive Clinical Review and Insights Into Underlying Involved Mechanisms.” JCEM. 1 Aug. 2017.