1493MO - Peripheral immune biomarkers of survival in patients with resectable dedifferentiated liposarcomas (DDLPS) and undifferentiated pleomorphic sarcomas (UPS) treated with neoadjuvant nivolumab +/- ipilimumab (neoICB)

Background

Recurrences are common after resection of DDLPS and UPS. We conducted a neoICB trial in resectable UPS and DDLPS pts and assessed peripheral immune biomarkers.

Methods

DDLPS (n=17) and UPS (n=10) patients (pts) were treated with neoICB; UPS pts received concurrent radiation. We performed RNA sequencing of peripheral blood mononuclear cells (PBMCs) and tumor specimens collected at baseline, on treatment and at surgery and single sample gene set enrichment analysis (ssGSEA) to quantify 30 immune cell types/signatures. The peripheral TCR repertoire (richness, clonality, density) was assessed by TCR-sequencing of DNA extracted from PBMCs. Correlation between peripheral and tumor immune scores were calculated by Spearman correlation test. Longitudinal comparisons between variables were done using ANOVA tests. Progression-free survival (PFS) was defined from time of neoICB start to progression on neoICB or relapse after surgery. Survival curves were compared using log-rank tests.

Results

Median follow-up was 30 months from start of ICB treatment. Median PFS was 20 months (DDLPS: 18 months; UPS: Not Reached), with 15 progression events (12 DDLPS, 3 UPS). None of the peripheral ssGSEA scores correlated with their tumor counterparts at any time point. There was no significant change in any peripheral ssGSEA score nor TCR richness or clonality upon ICB treatment. Peripheral TCR density decreased with ICB treatment (p<0.001; DDLPS: p=0.0037; UPS: p=0.0027). Pts with higher peripheral TCR densities (above median) on treatment had improved PFS (p=0.049). Higher peripheral TCR richness (above median) at baseline showed a trend towards better PFS (p=0.1) and was also seen on treatment (p=0.08) but not at surgery (p=0.81).

Conclusions

In UPS and DDLPS patients undergoing neoICB, we were unable to identify a correlation between peripheral and tumor immune cells and signatures. However, peripheral TCR richness and density at baseline and during treatment may identify pts with better prognosis.

Clinical trial identification

NCT03307616.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

BMS.

Disclosure

A. Reuben: Financial Interests, Personal, Advisory Board: Adaptive Biotechnologies. All other authors have declared no conflicts of interest.