1. In this study, patients who were obese or overweight had better survival compared to normal weight patients after receiving immune checkpoint blockade treatment for their cancer.

2. In patients with high tumor mutation burden, obesity was associated with greater response rate difference.

Evidence Rating Level: 2 (Good)

In patients with cancer, a phenomenon called the “obesity paradox” has been described, where obesity was surprisingly associated with better treatment outcomes. However, it is unclear whether this association is observed across cancer types and cancer therapy modalities. In the advent of immune checkpoint blockade therapy, whether and to what degree this association is present in this context is not well understood.

This prospective cohort study included 1840 adult cancer patients (57.55% male) at Memorial Sloan Kettering Cancer Center who had received at least 1 dose of immune checkpoint blockade (ICB) treatment from 2014 through 2019. The body mass index (BMI) of patients were measured within 30 days before treatment. The primary outcomes measured were overall and progression-free survival after ICB treatment.

Compared to patients with normal weight, both obese and overweight patients had better overall survival and progression-free survival. This analysis was further stratified based on number of tumor mutations (TMB) present at time of treatment. In both patients with high (>10) and lower number of tumor mutations (<10), obesity was associated with better overall and progression-free survival. Interestingly, the response rate difference between obese and normal weight patients was larger in patients with >10 TMBs compared to those with TMB <10. This study was limited in only having BMI as a measure of obesity, which could falsely categorize someone with higher muscle mass as “obese”. Therefore, which molecular sequelae of obesity underpins this observed association remains unclear. Nonetheless, this study highlighted an association between obesity and outcomes post immunotherapy for diverse types of cancers and suggest further work to be done to better elucidate the underpinning mechanism of this observation.

Click to read the study in JAMA Network Open 

Image: PD

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