Impact of obesity on immune-related adverse events and tyrosine kinase inhibitor side effects in patients with metastatic renal cell carcinoma (mRCC).

4560 Background: A pooled data analysis from clinical trials, including various cancer subtypes, showed that obesity is associated with a heightened incidence of immune-related adverse events (irAEs). However, the heterogeneous patient population across different demographics calls for further investigation into the correlation between obesity and adverse effects from immune checkpoint inhibitors (ICI) in mRCC. Additionally, there is limited available data regarding the association of obesity with tyrosine kinase inhibitors (TKIs) toxicities. We hypothesize that obesity may be linked to an increased rate of irAEs and TKIs toxicities in mRCC patients (pts). Methods: We conducted a retrospective analysis of pts diagnosed with mRCC using TriNetX Research Network (TriNetX LLC., Cambridge, Massachusetts, USA). We searched two cohorts (ICI and TKIs) and toxicities using the ICD-10-CM codes. Pts were categorized into two groups based on body mass index (BMI): obese (BMI ≥30) and non-obese (BMI >19 - < 30). Characteristics of the cohorts were balanced using propensity score matching. Results: A total of 4526 pts with mRCC receiving treatment met the inclusion criteria. 40% of pts were in ICI cohort (n=1811), and 60% (n=2715) in TKI cohort. In the ICI cohort 53% were obese (959/1811), and 47% non-obese (852/1811). Among both cohorts, 50% were male, 30% females, 20% unknown and the average age was 69-72. In TKI cohort, Obese group had 57% (1549/2715) pts while non-obese group included 43% (1166/2715) pts. In ICI cohort, there was no statistically significant difference in risk of developing thyroid dysfunction, liver toxicity, type 1 diabetes, adrenal insufficiency/hypophysitis, skin toxicity, pneumonitis, cardiomyopathy, colitis or myositis/arthropathy between obese and non-obese groups (p>0.05). In TKI cohort, risk of thyroid dysfunction was higher among obese (0.177, n=187/1056) vs non-obese (0.131, n=102/781), p=0.007. Moreover, obese pts had a higher rate of diarrhea compared to non-obese (0.141 vs 0.109, p= 0.017). No significant difference was seen in the rate of developing other toxicities including liver dysfunction, mucositis, cardiovascular toxicities including hypertensive crisis or fatigue. (Table) Conclusions: The use of TKIs has shown an increased risk of developing thyroid dysfunction and diarrhea in obese pts. However, there is no difference in irAE with use of ICI between obese and non-obese pts. Further large studies are needed to support this observation and to study the mechanism by which obesity and metabolic syndromes influence the development of adverse effects. [Table: see text]