Multi-omic analysis identifies hypoalbuminemia as independent biomarker of poor outcome upon PD-1 blockade in metastatic melanoma

Abstract

We evaluated the prognostic value of hypoalbuminemia in context of various biomarkers at baseline, including clinical, genomic, transcriptomic, and blood-based markers, in patients with metastatic melanoma treated with anti-PD-1 monotherapy or anti-PD-1/anti-CTLA-4 combination therapy (n=178). An independent validation cohort (n=79) was used to validate the performance of hypoalbuminemia compared to serum LDH (lactate dehydrogenase) levels. Pre-treatment hypoalbuminemia emerged as the strongest predictor of poor outcome for both OS (HR=4.01, 95% CI 2.10-7.67, Cox P=2.63e-05) and PFS (HR=3.72, 95% CI 2.06-6.73, Cox P=1.38e-05) in univariate analysis. In multivariate analysis, the association of hypoalbuminemia with PFS was independent of serum LDH, IFN-γ signature expression, TMB, ECOG PS, treatment line, treatment type (combination or monotherapy), brain and liver metastasis (HR=2.80, 95% CI 1.29-6.08, Cox P=0.00916). Our validation cohort confirmed the prognostic power of hypoalbuminemia for OS (HR=1.98, 95% CI 1.16-3.38; Cox P=0.0127) and was complementary to serum LDH in analyses for both OS (LDH-adjusted HR=2.12, 95% CI 1.2-3.72, Cox P=0.00925) and PFS (LDH-adjusted HR=1.91, 95% CI 1.08-3.38, Cox P=0.0261). In conclusion, pretreatment hypoalbuminemia was a powerful predictor of outcome in ICI in melanoma and showed remarkable complementarity to previously established biomarkers, including high LDH.