Multi-omic analysis identifies hypoalbuminemia as independent biomarker of poor outcome upon PD-1 blockade in metastatic melanoma
Lindsay V.M. Leek, Jessica C.L. Notohardjo, Karlijn de Joode, Eline L. Velker, John B.A.G. Haanen, Karijn P.M. Suijkerbuijk, Maureen J.B. Aarts, Jan Willem B. de Groot, Ellen Kapiteijn, Franchette W.P.J. van den Berkmortel, Hans M. Westgeest, Tanja D. de Gruijl, Valesca P. Retèl, Edwin Cuppen, Astrid A.M. van der Veldt, Mariëtte Labots, Emile E. Voest, Joris van de Haar, Alfons J.M. van den Eertwegh
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, age, ECOG PS, treatment line, treatment type (combination or monotherapy), brain and liver metastasis (HR = 2.76, 95% CI 1.24-6.13, Cox P = 0.0131). 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.