The impact of body mass index (BMI) on overall survival (OS) among patients receiving immune checkpoint inhibitors (ICIs): A population-based study.
Authors: Coyne Zac , Sutradhar Rinku , Aghanya Vivian , Kaliwal Yosuf , Niu Yue , Liu Ning , Liu Ying , Powis Melanie Lynn , Liu Geoffrey , Peppercorn Jeffrey M. , Krzyzanowska Monika K. , Eng Lawson 
Published: June 2024

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Background: While obesity is a risk factor for cancer, BMI has been previously identified as a potential prognostic marker in different solid tumors. Prior studies have identified that among cancer survivors receiving ICIs, higher BMI may be associated with better OS, but there have been heterogeneous results among studies. Here we use population-level administrative data to evaluate the association between BMI and OS among patients receiving ICIs. Methods: We used administrative data deterministically linked across databases to identify a cohort of solid tumors patients initiating ICI therapy in Ontario, Canada from June 2012 to October 2018 and obtained information on socio-demographics including BMI at start of ICI, clinical covariates, and OS. We applied multivariable Cox proportional hazards models to evaluate the impact of BMI on OS, adjusting for sex, age, cancer center, autoimmune history, recent hospitalization and comorbidity score. Subgroup analyses were performed based on disease site and sex. Results: Among 4863 patients, median age was 67, 57% male; 46% had lung cancer, 35% melanoma, 9% renal cancers; 40% received nivolumab, 36% pembrolizumab, 17% ipilimumab. Median BMI was 26.1, with 3% low, 29% normal, 27% overweight, 19% obese. Median OS 317 days. Overall, greater BMI was associated with better OS (aHR=0.98 per unit, 95% CI [0.97-0.99] p<0.001). When compared to normal BMI, obese (aHR=0.77 [0.70-0.85] P<0.001) and overweight patients (aHR=0.85 [0.78-0.93] p<0.001) had better OS while those with low BMI had poorer OS (aHR=1.39 [1.16-1.66] P<0.001). Among melanoma patients, those who were obese had better OS (aHR=0.84 [0.71-0.98] p=0.03) and low BMI patients had poorer OS (aHR=1.80 [1.20-2.69] p=0.004) when compared to normal BMI. For lung and renal patients, increased BMI was associated with better OS when BMI was evaluated continuously (aHRlung=0.99 per unit [0.98-1.00] p=0.05; aHRrenal=0.98 per unit [0.95-0.99] p=0.04), but no significant associations were observed when BMI was evaluated categorically (p>0.05). Among males, patients who were obese (aHR=0.70 [0.62-0.80] p<0.001) and overweight (aHR=0.80 [0.72-0.90] p<0.001) had better OS compared to those with normal BMI, while those with low BMI had poorer OS (aHR=1.58 [1.22-2.06] p<0.001). However, among females, low BMI were associated with poorer OS (aHR=1.29 [1.01-1.65] p=0.04) compared to normal BMI, while no significant associations with OS were observed for overweight (aHR=0.93,p=0.30) or obese (aHR=0.89, p=0.12) patients. Conclusions: BMI was identified as a potential prognostic factor among cancer survivors receiving ICIs where greater BMI was associated with better OS. This association varied by cancer type and sex and is particularly notable in melanoma and among males. Further studies understanding these prognostic associations are warranted.