1. Multi-omic analysis identifies hypoalbuminemia as independent biomarker of poor outcome upon PD-1 blockade in metastatic melanoma.
- Author
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Leek LVM, Notohardjo JCL, de Joode K, Velker EL, Haanen JBAG, Suijkerbuijk KPM, Aarts MJB, de Groot JWB, Kapiteijn E, van den Berkmortel FWPJ, Westgeest HM, de Gruijl TD, Retel VP, Cuppen E, van der Veldt AAM, Labots M, Voest EE, van de Haar J, and van den Eertwegh AJM
- Subjects
- Humans, Female, Male, Middle Aged, Aged, Prognosis, Programmed Cell Death 1 Receptor antagonists & inhibitors, Programmed Cell Death 1 Receptor metabolism, Adult, Neoplasm Metastasis, L-Lactate Dehydrogenase blood, L-Lactate Dehydrogenase metabolism, Aged, 80 and over, Multiomics, Melanoma drug therapy, Melanoma pathology, Melanoma metabolism, Hypoalbuminemia, Biomarkers, Tumor blood, Immune Checkpoint Inhibitors therapeutic use
- 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., (© 2024. The Author(s).)
- Published
- 2024
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