Abstract 73P
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 (≥ 1%).
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.
Resources from the same session
185P - Characterizing the metabolic reprogramming of mutant ß-catenin in hepatocellular carcinoma
Presenter: Nathalie Wong
Session: Poster Display session
Resources:
Abstract
186P - Unveil and overcome PD(L)1 antibody resistance via functional genomics and clinical derived biopsies
Presenter: BIN XIE
Session: Poster Display session
Resources:
Abstract
187P - Single-cell RNA sequencing elucidates the role of intercommunication between epithelial cells, immune cells, and fibroblasts in high-grade serous ovarian cancer
Presenter: Xiaoting Zhao
Session: Poster Display session
Resources:
Abstract
188P - Single-cell and spatial transcriptomics delineate the microstructure and immune landscape of intrahepatic cholangiocarcinoma in the leading-edge area
Presenter: Zuyin li
Session: Poster Display session
Resources:
Abstract
189P - Image-guided labeling of live cells in tertiary lymphoid structures for single-cell transcriptomics
Presenter: Mengrui Cao
Session: Poster Display session
Resources:
Abstract
190P - Ex vivo modeling of precision immuno-oncology responses in lung cancer
Presenter: Bassel Alsaed
Session: Poster Display session
Resources:
Abstract
191P - Patient-derived 3D-bioprinted tumours as a relevant and innovative tool for immunotherapeutic testing.
Presenter: Kamila Pawlicka
Session: Poster Display session
Resources:
Abstract
192P - A new neuroendocrine model and in vitro effect of melatonin and serotonin on the PD-L1 ligand and its immunomodulatory action
Presenter: Dulce Caraveo Gutiérrez
Session: Poster Display session
Resources:
Abstract
193P - Humanized mice applying CD47; Prkcd; IL2rg triple KO mice exhibit enhanced human immune cell engraftment and reduced GvHD symptoms
Presenter: Seung-Ho Heo
Session: Poster Display session
Resources:
Abstract
194P - The impact of BTK inhibitors on ?d T cell fitness: Lesson for immunotherapy
Presenter: Adam Michalski
Session: Poster Display session
Resources:
Abstract