TY - JOUR
T1 - Multi-omic analysis identifies hypoalbuminemia as independent biomarker of poor outcome upon PD-1 blockade in metastatic melanoma
AU - Leek, Lindsay V.M.
AU - Notohardjo, Jessica C.L.
AU - de Joode, Karlijn
AU - Velker, Eline L.
AU - Haanen, John B.A.G.
AU - Suijkerbuijk, Karijn P.M.
AU - Aarts, Maureen J.B.
AU - de Groot, Jan Willem B.
AU - Kapiteijn, Ellen
AU - van den Berkmortel, Franchette W.P.J.
AU - Westgeest, Hans M.
AU - de Gruijl, Tanja D.
AU - Retel, Valesca P.
AU - Cuppen, Edwin
AU - van der Veldt, Astrid A.M.
AU - Labots, Mariette
AU - Voest, Emile E.
AU - van de Haar, Joris
AU - van den Eertwegh, Alfons J.M.
N1 - Publisher Copyright: © The Author(s) 2024.
PY - 2024/5/16
Y1 - 2024/5/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85193480089&partnerID=8YFLogxK
U2 - 10.1038/s41598-024-61150-y
DO - 10.1038/s41598-024-61150-y
M3 - Article
C2 - 38755213
AN - SCOPUS:85193480089
SN - 2045-2322
VL - 14
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 11244
ER -