566
Background: An elevated BMI is associated with improved survival in mRCC patients treated with oral targeted therapies (TT); however, this relationship in the contemporary treatment landscape is unknown. We investigated the effect of BMI on outcomes in mRCC patients treated with PD-1/PD-L1 ICB. Methods: We analyzed 147 patients with mRCC who received ICB alone or in combination with VEGF or other therapies. The association of BMI with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) was evaluated using logistic and Cox regression models, adjusted for known prognostic factors including International Metastatic RCC Database Consortium (IMDC) risk groups, line of therapy, ECOG (0 vs ≥1), and histology. Results: Median follow up was 25.5 (4.3-78.6) months (mos). Median time on ICB was 5.1 ( < 0.1-69.7) mos. Overall, most patients were male (71%), had clear cell histology (85%), and were intermediate risk (60%). 43% received first-line ICB and 45% received ICB in combination therapy (37% with VEGF inhibition, 8% with other therapies). At ICB initiation, 46 (31%) patients were considered underweight/normal weight (BMI < 25 kg/m
2
), 56 (38%) overweight (BMI 25-30 kg/m
2
), and 45 (31%) obese (BMI > 30 kg/m
2
). Patients with high BMI (≥ 25) had improved OS (median 34.3 vs 16.7 mos, 2-yr OS 61 vs 42%, p = 0.016) compared to those with low BMI ( < 25), with an adjusted hazard ratio (HR) = 0.74 (0.44-1.26). ORR (33 vs 28%, p = 0.7) and PFS (median 8.2 vs 5.9 mos, p = 0.4) did not statistically differ. Patients who experienced a BMI change from ≥ 25 at start of first-line TT to < 25 at start of subsequent-line ICB displayed shorter OS (adjusted HR = 2.25 (0.94-5.35)) compared to those with no change. Conclusions: High BMI appears to be associated with improved OS in mRCC patients treated with ICB. This contemporary data is consistent with the “obesity paradox” demonstrated in the TT era. Validation with the IMDC database and examination of underlying mechanisms are ongoing.