Association between body mass index (BMI) and anti-PD1/L1 immune checkpoint inhibitor (ICI) outcomes in patients with metastatic urothelial carcinoma (mUC)

Anti-PD1/L1 ICIs are indicated for mUC, however, only a minority of patients (pts) will derive therapeutic benefit. Strong predictive and prognostic factors are lacking. Obesity causes a low grade chronic inflammatory state and has been associated with increased ICI responsiveness in some cancer types. We investigated whether elevated BMI was associated with ICI outcomes in mUC. We performed a multi-center retrospective cohort study including 121 pts with mUC who received anti-PD1/L1 ICI for metastatic disease between 2016-2021 at 3 Canadian cancer centres. Clinical characteristics, including demographics, BMI, neutrophil to lymphocyte ratio (NLR), objective response, and survival were abstracted from chart review. ICI treatment response was determined by investigator assessment of clinical and radiologic parameters. Fisher’s exact test was used to assess differences in response rates between groups. Log rank and Cox regression models were used to assess overall survival (OS). Ninety (74%) were male, and 74 (61%) received ICI as a 2nd or later line therapy for metastatic disease. Twenty-three pts had a BMI ≥ 30, 43 had a 25 ≤ BMI < 30 and 55 had a BMI < 25. A BMI ≥ 25 was significantly correlated to a higher response rate to ICI (45.4% vs 16.3%, p=0.02). After a median follow-up of 14.5 months, pts with BMI ≥ 30 experienced significant longer median OS 24.8 months vs 14.4 months for 25 ≤ BMI < 30 and 8.5 months for BMI < 25 (p=0.012). In multivariate analysis, BMI ≥ 30 was an independent prognosis factor for OS as detailed in the table.Table: 1754POSUnivariableMultivariableHR95%CIp-valueHR95%CIp-valueBMI ≥ 30 vs < 300.630.45-0.880.0020.400.17-0.960.040Male vs Female0.950.58-1.570.867ECOG ≥ 2 vs 0-11.680.86-3.290.1252.211.02-4.780.042ICI Line ≥ 2 vs 12.391.43-3.970.0011.801.31-2.480.000NLR ≥ 4 vs < 42.461.53-3.940.0002.661.58-4.490.000Bone metastasis Yes vs No2.381.52-3.730.0001.981.17-3.350.010Lung metastasis Yes vs No1.881.21-2.930.005Liver metastasis Yes vs No1.921.20-3.090.006Age ≥ 60 vs < 601.880.65-5.450.235 Open table in a new tab Our data identified BMI, as a novel potential biomarker that is strongly and independently associated with ICI response and survival in mUC. External validation of these data in a larger study and investigations into the mechanisms behind these findings are warranted.