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 - Funding Information:
We thank all patients and their families for participating in the present study. This work was funded by the Technology Assessment of Next Generation Sequencing in Personalized Oncology (TANGO) initiative from ZonMw (846001002). We would also like to thank the Centre for Personalized Cancer Treatment\u00A0and the Hartwig Medical Foundation for generating the genomics data used for this study.
Funding Information:
A.v.d.V has consultancy relationships with BMS, MSD, Roche, Novartis, Pfizer, Ipsen, Eisai, Pierre Fabre, and Sanofi, all paid to the institute. E.E.V. is a supervisory board member of the Hartwig Medical Foundation. E.K. has consultancy/advisory relationships with Bristol Myers Squibb, Novartis, Merck, Pierre Fabre, Lilly, and Bayer not related to current work and paid to institute, and received research grants not associated with this paper from Bristol Myers Squibb, Delcath, and Pierre-Fabre. J.H. has provided consultation, attended advisory boards, and/or provided lectures for BMS, CureVac, GSK, Imcyse, Iovance Bio, Instil Bio, Immunocore, Ipsen, Merck Serono, MSD, Molecular Partners, Novartis, Pfizer, Roche/Genentech, Sanofi, Scenic, Third Rock Ventures, has participated in the SAB of Achilles Tx, BioNTech US, Instil Bio, PokeAcell, T-Knife, Scenic and Neogene Therapeutics. Through this, the NKI has received grant support from Amgen, Asher Bio, BioNTech, BMS, MSD, Novartis, and Sastra Cell Therapy. MA has advisory board/consultancy honoraria from Amgen, Bristol Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Astellas, and Bayer. J.H has received research grants from Merck-Pfizer that were paid to the institute and not related to current work. M.A. has advisory board/consultancy honoraria from Amgen, Bristol Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Astellas, and Bayer. Research grants Merck-Pfizer. Not related to current work and paid to the institute. F.v.d.B receives a speaker fee for Merck. Not related to current work and paid to the institute. The other authors reported no disclosures.
Funding Information:
Funding was provided by ZonMw (Grant numbers: 846001002, 846001002, 846001002).
Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12/1
Y1 - 2024/12/1
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-? 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-? 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.
U2 - 10.1038/s41598-024-61150-y
DO - 10.1038/s41598-024-61150-y
M3 - Article
SN - 2045-2322
VL - 14
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 11244
ER -