OR28-07 Increased BMI Is Associated With Anti PD-1/PD-L1-Induced Thyroid Immune-Related Adverse Events

Background: Immune checkpoint inhibitors have revolutionized cancer therapy, however, are associated with immune related adverse events (irAEs). Obesity is a pro-inflammatory metabolic state that may play a role in the development of irAEs. Hypothesis: We hypothesized that likelihood of developing thyroid irAEs following anti-PD-1/L1 therapy increases with increasing body mass index (BMI). Methods: We retrospectively analyzed data of 187 cancer patients who initiated anti-PD-1/L1 at our institution between 01/2014-12/2018, had normal thyroid function tests at baseline and had baseline BMI data available. Results: Overall, 97 (52.2%) patients were with low-normal BMI (<25 kg/m(2)), 52 (28.0%) overweight (≥25-30 kg/m(2)) and 37 (19.9%) obese (≥30 kg/m(2)). Thyroid dysfunction (hyper or hypo, overt or subclinical) developed in 72/187 (38.7%) patients, of whom 29/97 (29.9%) had low-normal BMI, 22/52 (42.3%) were overweight and 21/37 (56.8%) obese (p=0.14). With every 1 kg/m(2) increase in BMI, the likelihood of thyroid dysfunction increased by 8.8% (p=0.004). Overt hyperthyroidism occurred in 32/186 (9.1%) of the patients - in 4.1% of patients with low-normal BMI, 11.5% of overweight patients and 18.9% of obese (p=0.006). Overt hypothyroidism occurred in 32/186 (17.2%) of the patients and was not significantly associated with BMI. Hyperthyroidism followed by overt hypothyroidism, consistent with thyroiditis, occurred in 13/186 (7.0%) of patients and was significantly associated with increasing BMI category (p=0.03). Conclusions: Increased BMI was associated with increased thyroid irAEs in patients treated with PD-1/L1 inhibitors. Further exploration of the interaction between obesity and immunotherapy may provide insight into the role of inflammation in mediating immune response.