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. 2025 May 15:221:115402.
doi: 10.1016/j.ejca.2025.115402. Epub 2025 Apr 1.

Impact of assessment-to-treatment interval and metastatic biopsy site on the predictive value of PD-L1 expression at the 1 % cut-off level in melanoma

Cecilie D Vestergaard  1 , Marco Donia  1 , Kasper Madsen  1 , Henrik Schmidt  2 , Adam A Luczak  3 , Lars Bastholt  4 , Eva Ellebaek  1 , Inge M Svane  5
Affiliations
Free article

Impact of assessment-to-treatment interval and metastatic biopsy site on the predictive value of PD-L1 expression at the 1 % cut-off level in melanoma

Cecilie D Vestergaard et al. Eur J Cancer. .
Free article

Abstract

Background: Intratumoral PD-L1 expression at the 1 % cut-off predicts clinical outcomes and may guide first-line immune checkpoint inhibitor (ICI) selection for metastatic melanoma (MM). However, the impact of the interval between PD-L1 assessment and ICI initiation and the metastatic site used for PD-L1 evaluation, remains unclear.

Methods: In this nationwide cohort study we used the Danish Metastatic Melanoma Database (DAMMED) and the Danish Pathology Registry to analyze patients with MM treated with anti-PD-1 or anti-PD-1 plus anti-CTLA-4 from January 2017 to February 2024. Progression-free survival (PFS) and overall survival (OS) were analyzed using Log-rank tests and Cox regression.

Results: Data from 1137 patients were analyzed. Among patients with PD-L1 assessed within 90 days of treatment (n = 964; 55.2 % PD-L1 <1 %, 44.8 % PD-L1 ≥1 %), combination therapy improved outcomes in PD-L1 < 1 % (PFS adjusted (a)HR 0.62; 95 % CI 0.48-0.80; p < 0.001, OS aHR 0.64; 95 % CI 0.48-0.85; p = 0.002), while outcomes were comparable for PD-L1 ≥ 1 % patients (PFS aHR 0.90; 95 % CI 0.62-1.30; p = 0.57, OS aHR 0.97; 95 % CI 0.60-1.57; p = 0.89). For PD-L1 assessed > 90 days prior (n = 173), this pattern was less pronounced. Among 48 paired PD-L1 assessments from the same organ, discordance occurred in 25 %. Combination therapy improved PFS for patients with PD-L1 < 1 % skin/subcutaneous (aHR 0.51; 95 % CI 0.34-0.76; p < 0.001) and visceral metastases (aHR 0.65; 95 % CI 0.42-1.02; p = 0.060) while this association was not evident for lymph node metastases (aHR 0.79; 95 % CI 0.48-1.29; p = 0.35).

Conclusions: PD-L1 seems a reliable predictive biomarker in MM, when assessed on tissue obtained within 90 days prior to ICI initiation. Non-nodal metastatic sites appear preferable.

Keywords: Anti-CTLA-4; Anti-PD-1; Immunotherapy; Metastatic melanoma; PD-L1 status; Predictive biomarker; Real-world Evidence.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MD has received advisory fees from Achilles Therapeutics, and consultancy fees via membership of Guidepoint LLC and Alphasights expert network. HS received honoraries for consultancies and lectures from Novartis, Merck, Bristol-Myers Squibb, and Incyte; and restricted research grants from MSD. LB served on the advisory board of Bristol-Myers Squibb, Roche, Novartis, Merck, EISAI, and Bayer Healthcare. IMS has received honoraria for consultancies and lectures from Novartis, Roche, Merck, and Bristol Myers Squibb; a restricted research grant from Novartis; and financial support for attending symposia from Bristol Myers Squibb, Merck, Novartis, Pfizer, and Roche. EE received honoraries for consultancies and lectures from Novartis, Merck, Bristol-Myers Squibb, and Pierre Fabre, and conference and travel coverage from Pierre Fabre and Merck. All remaining authors have declared no conflicts of interest.

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