The relationship between obesity and immunotherapy: It's complicated.

Abstract

9562 Background: Obesity is a poor prognostic factor in primary melanoma, and preclinical data has linked it to an immunosuppressive phenotype. Paradoxically, recent reports suggest that obesity may confer a survival benefit in patients with metastatic melanoma (MM) who received immune checkpoint inhibition (ICI). Herein we tested the hypothesis that the relationship between body mass index (BMI) and response to ICI depends on type of ICI and tumor type. Methods: We examined 2 cohorts (MM patients [n = 423] and metastatic bladder cancer [MBC] patients [n = 42]). We tested the associations between BMI and PFS, stratified by first vs. second or greater-line of treatment and treatment type (anti-CTLA4, anti-PD1, combination therapy), adjusting for age, gender, stage, LDH level, ECOG status, number of metastatic sites, and BMI classification changes in the MM cohort. Results: We observed a moderate but insignificant association between being overweight (BMI 25.0-29.9 kg/m2) or obese (BMI > 30kg/m2) and better PFS in patients who received first line ICI therapy (aHR 0·77 [95% CI 0·50-1·20]), and an association with worse PFS in patients who received non-first line ICI therapy (aHR 1.31 [0·74-2.33], P interaction = 0.11). Overweight and obese patients receiving combination ICI had a statistically significant survival benefit (aHR 0.27 [0·10-0.70]), p = 0.007), whereas patients receiving the other treatment types showed heterogeneous trends (P interaction = .005). In the MBC cohort, being overweight conferred the greatest PFS benefit, followed by normal BMI, with obesity being associated with the worst PFS (p = 0.035). Conclusions: Stratifying by clinical features including treatment type, treatment line, and tumor type demonstrated vastly different results and reversal of trends, which underpins the complexity of the relationship between BMI and response to ICI. The lack of consistency amongst our data and published reports highlights the need for a thorough investigation, on a significantly larger scale, to truly elucidate obesity's impact on clinical outcomes in cancer. The scientific community must consider this complexity as well as the known detrimental health effects of obesity when counseling patients.