Body Composition and Inflammation as Emerging Sex-Specific Prognostic Factors in Patients with Advanced Cutaneous Melanoma Undergoing Immune Checkpoint-Inhibition Therapy: A Prospective Pilot Study.

Introduction: The distribution of muscle and adipose tissues masses physiologically follow sex-specific patterns. On the other hand, the clinical and biological consequences of pathologic body composition, i.e., sarcopenia or obesity, also depend on tissue distribution patterns. Although obesity-associated inflammation has been correlated with survival benefits of cancer patients undergoing immune checkpoint inhibition (ICI) therapy, detailed and sex-specific body composition analyses are widely missing. Here, we prospectively analyzed body composition and serum parameters of inflammation and protein metabolism in patients with advanced melanoma before and 3 months after initiation of ICI therapy.

Methods: Between 2016 and 2018, consecutive patients with advanced cutaneous melanoma were recruited into the study at our cancer center (Skin Cancer Center, CIO, University Hospital Cologne, Germany). Blood samples and body composition based on bioelectrical impedance analysis (BIA) were assessed before ICI therapy initiation (T1) and after 3 months (T2). Correlation of blood parameters with body composition as well as progression-free (PFS) and overall survival (OS) was analyzed in sex-specific subgroups.

Results: From a total of 54 patients, 25 were women and 29 were men. In women, a high muscle mass at T1 was the strongest marker for longer PFS (HR 0.84; 95% CI: 0.74-0.98; p = 0.024), while in men (n = 29), high phase angle values at T1 correlated with significantly longer PFS (HR 0.48; 95% CI: 0.26-0.90; p = 0.023). Regarding OS, muscle mass status at T1 remained the strongest predictor for longer survival in women (HR 0.85; 95% CI: 0.72-0.99; p = 0.033), while in men, increased leukocyte blood counts at T1 were associated with the poorest OS (HR 1.36; 95% CI: 1.14-1.62; p = 0.001). Inflammation and the immuno-nutritional score mGPS correlated with body composition parameters in a sex-specific manner. However, we did not observe an impact of dynamic changes between T1 and T2 in all analyzed parameters.

Conclusion: Our data suggest that BIA-derived markers are associated with the prognosis of melanoma patients undergoing ICI therapy in a sex-specific manner. Selected body composition parameters correlate differently with blood markers of inflammation and protein metabolism in men and women. If validated in larger trials, these assessments might improve individualized supportive care and clinical risk stratification.