Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab.
- 2020
Available online from MWHC library: 1995 - present (after 1 year), Available in print through MWHC library: 1999 - February 2003
CONCLUSIONS: We show that quantitative assessments of CD8+ CD3+ PD-1+ T cells, % TAMs expressing PD-L1, and other T cell densities correlate with sarcoma response to pembrolizumab and improved PFS. Our findings support that multiple cell types present at the start of treatment may enhance tumor regression following anti-PD-1 therapy in specific advanced sarcomas. Efforts to confirm the activity of pembrolizumab in an expansion cohort of UPS/DDLPS patients are underway. Copyright (c)2020, American Association for Cancer Research. EXPERIMENTAL DESIGN: Pretreatment (n=78) and 8-week on-treatment (n=68) tumor biopsies were stained for PD-L1 and multiplex immunofluorescence panels. The density of positive cells was quantified to determine associations with anti-PD-1 response. PURPOSE: We recently reported a 17.5 % objective RECIST 1.1 response rate in a Phase II study of pembrolizumab in patients with advanced sarcoma (SARC028). The majority of responses occurred in undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated liposarcoma (DDLPS). We sought to determine whether we can identify immune features that correlate with clinical outcomes from tumor tissues obtained pre- and on-treatment. RESULTS: Patients that responded to pembrolizumab were more likely to have higher densities of activated T cells (CD8+ CD3+ PD-1+) and increased percentage of tumor associated macrophages (TAMs) expressing PD-L1 pre-treatment compared to non-responders. Pre-treatment tumors from responders also exhibited higher densities of effector memory cytotoxic T cells and regulatory T cells compared to non-responders. Additionally, higher density of cytotoxic tumor infiltrating T-cells at baseline correlated with a better progression-free survival (PFS).