1492MO Immune and vascular biomarkers associated with efficacy and mechanism of actions of the combination of lenvatinib (L) and eribulin (E) in leiomyosarcoma (LMS) and liposarcoma (LPS)

The interactions with immune system and influence on the tumor microenvironment (TME) of L + E remain elusive. LEADER study (NCT03526679) investigated efficacy in advanced LMS LPS immune-related biomarkers were examined. Pre- post-treatment (2 cycles) samples analyzed using nCounter Platform by Nanostring PanCancer Immune Profiling Panel including 760 genes associated cells regulations. Analyses based gene expression levels cells, which was estimated transcriptomic-based methods (MCP-Counter or Danaher et al. 2017). 32 (11 pre-post paired) had adequate quality for analysis; there 4 15 pts, PR SD as best response; 13 pts PFS ≥ 6 months. Based pretreatment samples, higher endothelial significantly (p = 0.027). Bundled pre (n 19) vs post (n=13)-treatment analysis showed a significant increase dendritic after 0.037). In paired patients longer than months increased 0.031), Th1 macrophages 0.016), cytotoxic 0.047), exhausted CD8 0.047). Results differential also suggested similar pattern transformation into an active TME +E: mRNA TNFSR14 0.03) CCL19 0.03), both are molecules tertiary lymphoid structure, increased. L+E may have ability to adjust TME. A pre-treatment immune-suppressive worse clinical efficacy, but transformed immune-active better outcome.