학술논문
Multi-omic analysis identifies hypoalbuminemia as independent biomarker of poor outcome upon PD-1 blockade in metastatic melanoma.
Document Type
Article
Author
Leek, Lindsay V. M.; Notohardjo, Jessica C. L.; de Joode, Karlijn; Velker, Eline L.; Haanen, John B. A. G.; Suijkerbuijk, Karijn P. M.; Aarts, Maureen J. B.; de Groot, Jan Willem B.; Kapiteijn, Ellen; van den Berkmortel, Franchette W. P. J.; Westgeest, Hans M.; de Gruijl, Tanja D.; Retel, Valesca P.; Cuppen, Edwin; van der Veldt, Astrid A. M.; Labots, Mariette; Voest, Emile E.; van de Haar, Joris; van den Eertwegh, Alfons J. M.
Source
Subject
*MELANOMA
*PROGRAMMED cell death 1 receptors
*LIVER metastasis
*BIOMARKERS
*METASTASIS
*PROGRESSION-free survival
*
*
*
*
*
Language
ISSN
2045-2322
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. [ABSTRACT FROM AUTHOR]