Subcutaneous Fat Abundance and Density Are Associated with an Enhanced Response to Immunotherapy in Metastatic Melanoma: A Retrospective Cohort Study

Rationale and Objectives: Despite the impressive efficacy of immune checkpoint inhibitors (ICIs) in the treatment of metastatic melanoma, not all patients respond to therapy. In addition, ICI harbors the risk for serious adverse events (AEs), highlighting the need for novel biomarkers predicting treatment response and occurrence of AEs. Recently, the identification of enhanced response to ICI in obese patients has indicated that body composition might influence treatment efficacy. The aim of the current study is to assess radiologic measurements of body composition as biomarkers for treatment response and AEs to ICI in melanoma. Materials and Methods: In the current work, we analyze adipose tissue abundance and density, as well as muscle mass via computed tomography scans in a retrospective cohort of 100 patients with non-resectable stage III/IV melanoma receiving first-line treatment with ICI in our department. From these, we investigate the impact of the subcutaneous adipose tissue gauge index (SATGI) and other parameters of body composition on treatment efficacy and occurrence of AEs. Results: Low SATGI was associated with prolonged progression-free survival (PFS) in univariate and multivariate analyses (hazard ratio 2.56 [95% CI 1.18-5.55], P=.02), as well as an enhanced objective response rate (50.0% vs 27.1%; P=.02). Further analysis with a random forest survival model highlighted a nonlinear relationship between SATGI and PFS with a clear separation into high- and low-risk cohorts separated by the median. Finally, a significant enrichment of cases with vitiligo, but no other AEs, was observed in the SATGI-low cohort (11.5% vs 0%; P=.03). Conclusion: We identify SATGI as a biomarker predicting treatment response to ICI without increased risk for severe AEs in melanoma.

Automated summary

This study aims to evaluate radiologic measurements of body composition as biomarkers predicting treatment response and adverse events (AEs) in melanoma patients receiving immune checkpoint inhibitors (ICI). The study found that low subcutaneous adipose tissue gauge index (SATGI) was associated with prolonged progression-free survival (PFS) and enhanced objective response rate. In addition, a significant enrichment of cases with vitiligo was observed in the SATGI-low cohort.