Before-treatment body mass index as a prognostic factor in cancer patients receiving immune checkpoint inhibitors: a systematic review and dose-response meta-analysis
Abstract
Pretreatment body mass index (BMI) has been associated with outcomes during immune checkpoint inhibitor (ICI) therapy, but study-specific categories and incomplete adjustment complicate interpretation. We evaluated associations with efficacy and toxicity across tumor types and BMI definitions. We searched the Cochrane Library, Embase, PubMed, and Web of Science from inception through November 30, 2025. Random-effects models pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for objective response rate (ORR) and immune-related adverse events (irAEs). Adjusted estimates defined the primary analyses. We also evaluated category-specific contrasts, clinical subgroups, cutoff meta-regression, and linear dose-response associations per 5-kg/m 2 increase in BMI. Sixty-one studies involving 46,572 patients were included. Higher BMI was associated with a lower adjusted hazard of death (HR = 0.74, 95% CI: 0.67-0.82, P < 0.001; I 2 = 70.6%; 95% prediction interval: 0.48-1.13) and a lower adjusted hazard of progression or death (HR = 0.78, 95% CI: 0.69-0.89, P < 0.001; I 2 = 60.3%; 95% prediction interval: 0.47-1.32). However, both prediction intervals included the null value. Category-specific analyses showed that obesity, but not overweight, was associated with improved OS and PFS relative to normal weight. BMI cutoff did not significantly moderate either endpoint. Per 5-kg/m 2 increase in BMI, adjusted PFS improved (HR = 0.87, 95% CI: 0.81-0.95, P < 0.001; I 2 = 47.7%), whereas OS did not (HR = 0.91, 95% CI: 0.81-1.01, P >0.05; I 2 = 64.0%). Adjusted associations with ORR and any-grade irAEs were not significant, and evidence for grade 3 or higher irAEs was insufficient. In this systematic review and meta-analysis, higher pretreatment BMI was associated with longer adjusted OS and PFS in patients receiving ICIs, with the most consistent favorable association observed for obesity. However, the prediction intervals included the null value, and associations with treatment response and irAEs remained inconsistent, warranting cautious interpretation.