Body composition and checkpoint inhibitor treatment outcomes in advanced melanoma: a multicenter cohort study

Background The association of body composition with checkpoint inhibitor outcomes in melanoma is a matter of ongoing debate. In this study, we aim to investigate body mass index (BMI) alongside computed tomography (CT)-derived body composition metrics in the largest cohort to date. Methods Patients treated with first-line anti-PD1 ± anti-CTLA4 for advanced melanoma were retrospectively identified from 11 melanoma centers in The Netherlands. From baseline CT scans, 5 body composition metrics were extracted: subcutaneous adipose tissue index, visceral adipose tissue index, skeletal muscle index, density, and gauge. These metrics were correlated in univariable and multivariable Cox proportional hazards analysis with progression-free survival, overall survival, and melanoma-specific survival (PFS, OS, and MSS). Results A total of 1471 eligible patients were included. Median PFS and OS were 9.1 and 38.1 months, respectively. Worse PFS was observed in underweight patients (multivariable hazard ratio [HR] = 1.86, 95% CI = 1.14 to 3.06). Furthermore, prolonged OS was observed in patients with higher skeletal muscle density (multivariable HR = 0.88, 95% CI = 0.81 to 0.97) and gauge (multivariable HR = 0.61, 95% CI = 0.82 to 0.998), whereas higher visceral adipose tissue index was associated with worse OS (multivariable HR = 1.12, 95% CI = 1.04 to 1.22). No association with survival outcomes was found for overweight, obesity, or subcutaneous adipose tissue. Conclusion Our findings suggest that underweight BMI is associated with worse PFS, whereas higher skeletal muscle density and lower visceral adipose tissue index were associated with improved OS. These associations were independent of known prognostic factors, including sex, age, performance status, and extent of disease. No significant association between higher BMI and survival outcomes was observed.