73P - Impact of Assessment-to-Treatment Interval on the Predictive Value of PD-L1 Expression in Melanoma

Background

A PD-L1 expression ≥ 1% in tumor tissue from patients with metastatic melanoma is associated with improved survival and may serve as a tool for selecting the optimal first-line immune checkpoint inhibitor (ICI) regime. However, the impact of the interval between PD-L1 assessment and ICI initiation on its predictive value remains unclarified.

Methods

In this national population-based study, we combined the Danish Metastatic Melanoma Database, that holds data on all Danish patients diagnosed with metastatic melanoma, and the Danish Pathology Register, containing date of PD-L1 assessments on tumor biopsies. Patients who initiated anti-PD-1-based therapy, either anti-PD-1 alone or anti-PD-1 plus anti-CTLA-4, for metastatic melanoma between January 2017 and February 2024 were included. We evaluated progression-free survival (PFS) and overall survival (OS) using Log-rank test. The primary objective was to determine whether the time between latest biopsy with a PD-L1 assessment and ICI initiation (≤/> 90 days) affected the predictive value of PD-L1 expression (

Results

We identified 1137 eligible patients (648 PD-L1 < 1%, 489 PD-L1 ≥ 1%). 143 individuals, with more than one biopsy assessed for PD-L1 expression showed shifting PD-L1 levels: 29% changed from < 1% to ≥ 1%, while 30% changed from ≥ 1% to < 1%. In cases where assessment-to-treatment interval was less than 90 days, patients with PD-L1 ≥ 1% tumor biopsies did not benefit from combination ICI treatment compared to anti-PD-1 monotherapy, while patients with PD-L1 < 1% tumors did (median PFS 13.6 vs. 7.1 months, HR 0.63, 95% CI 0.51-0.77, p<0.0001, median OS not reached vs. 24.3 months, HR 0,57, 95% CI 0.45-0.74, p<0.0001). When the interval exceeded 90 days, neither the patients with PD-L1 < 1% nor ≥ 1% significantly benefitted from combination therapy.

Conclusions

The predictive validity of PD-L1 expression is influenced by the time interval between biopsy and ICI initiation. Dynamic changes in PD-L1 expression over time can influence the results. PD-L1 assessment older than 90 days should not be used for treatment guidance.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

C.D. Vestergaard: Other, Personal, Funding, Travel grant: Novartis. M. Donia: Financial Interests, Personal, Other, Advisor: Achilles Therapeutics; Financial Interests, Personal, Other, Advisor (not for pharmaceutical companies): Guidepoint Global LLC, Alphasights; Other, Personal, Other, Chairman of the Melanoma and Non-melanoma Skin Cancer Scientific Committee: Danish Medicines Council (Medicinrådet). H. Schmidt: Other, Personal, Research Grant: MSD. L. Bastholt: Non-Financial Interests, Personal, Advisory Role, Scientific committee under Danish Medicines Agency regarding new treatments of melanoma, skin cancer and thyroid cancer; Danish Medicines Agency. E. Ellebaek: Financial Interests, Personal, Invited Speaker: Pierre Fabre, BMS, Novartis, MSD, Pfizer; Other, Personal, Other, Travel and conference expenses: MSD, Pierre Fabre. I.M. Svane: Financial Interests, Personal, Advisory Board: Novartis, Mendus, Instil Bio; Financial Interests, Personal, Invited Speaker: MSD, BMS, Sanofi, Takeda; Financial Interests, Personal, Writing Engagement: MSD; Financial Interests, Personal, Stocks/Shares, Cofounder and Founder warrants: IO Biotech; Financial Interests, Institutional, Research Grant: Adaptimmune, Enara Bio, Lytix Biopharma, TILT Biotherapeutics, Asgard Therapeutics, IO Biotech; Financial Interests, Institutional, Funding: Evaxion; Financial Interests, Institutional, Other, drug for investigator driven trial: BMS; Non-Financial Interests, Personal, Principal Investigator: BMS, Roche, TILT Biotherapeutics, Lytix Biopharma, Novartis, Immunocore, MSD. All other authors have declared no conflicts of interest.