Effect of body mass index on the efficacy of immune checkpoint inhibitors in patients with advanced cancer: Is the obesity paradox real?

Abstract Background: Recent studies have shown that an increased body mass index (BMI) is associated with an improved response to immune checkpoint inhibitors (ICIs). We evaluated the association between BMI and response to the ICIs in solid tumors. Methods: We retrospectively analyzed patients with advanced cancer treated with ICIs at one academic center between 2014-2022. We calculated the BMI based on the weight of the patients when they started ICI treatment and divided the patients into two groups: underweight/normal weight (BMI < 25) and overweight/obese (BMI ≥ 25) and compared the treatment responses between these two groups. After excluding underweight patients, we also compared the progression-free survival (PFS) and overall survival (OS) of normal-weight, overweight, and obese patients. Results: Overall, 130 patients were evaluated. The median age was 61, and 83.8% were male. 53 (40.7) patients had BMI <25 and 77 (59.3) patients had a BMI ≥ 25. In underweight/normal patients, median PFS was 7.7 months (95% CI: 4.9–10.4) vs 8.7 months (95% CI: 2.6–14.9) in overweight/obese patients (HR 1.03, 95% CI: 0.69–1.53), p = 0.865). In underweight/normal patients, the median OS was 22.1 months (95% CI: 11.1-33.1) compared to 21.3 months (95% CI: 13.8–28.8) in overweight/obese patients (HR 1.02, 95% CI: 0.67–1.57, p = 0.898). The objective response rate (ORR) was 39.6% in underweight/normal patients and 40.3% in overweight/obese patients (p = 0.942). After excluding underweight patients, there were also no significant differences in PFS (p = 0.962), OS (p = 0.609), and ORR (p = 0.815) between patients of normal weight, overweight, and obesity. Conclusion: In patients with advanced cancer treated with ICIs, there is no impact of BMI on PFS, OS, or ORR. Prospective studies are required to evaluate the prognostic impact of dynamic changes of BMI on the response to ICIs.