191P Fecal microbiome in soft-tissue sarcoma (STS) patients treated with neoadjuvant immune checkpoint blockade (ICB)

Abstract

BackgroundThe fecal microbiome is associated with toxicity and efficacy of ICB in multiple malignancies, although little is known about its role in STS. We examined the impact of the fecal microbiome on toxicity and early relapse in a phase II trial of neoadjuvant ICB for extremity/truncal undifferentiated pleomorphic sarcoma (UPS) and retroperitoneal dedifferentiated liposarcoma (DDLPS).MethodsPatients (DDLPS, n=17; UPS, n=10) were randomized to receive neoadjuvant nivolumab or nivolumab/ipilimumab, with UPS patients receiving ICB/radiation therapy concurrently. Fecal samples were collected at baseline, after 1 cycle of ICB, and at surgery. Fecal microbiomes were profiled via 16S rRNA gene sequencing and operational taxonomic units determined with UPARSE and the SILVA database. Comparisons were made using alpha and beta diversity scores and taxonomic relative abundances to evaluate differences between the two sarcoma types, patients with early or late relapse, and for those with immune-mediated toxicity, carried out with non-parametric statistical tests.ResultsFecal microbiomes from DDLPS and UPS patients were found to have similar diversity, composition, and structure at baseline (p=0.431). Fecal microbiomes from both histotypes were characterized by an abundance of Bacteroides sp. and Blautia sp; however, baseline samples from patients with UPS had a higher relative abundance of Faecalibaterium sp. when compared to DDLPS (7.5% vs. 4.7%; p=0.038). Patients that experienced immune-mediated diarrhea or colitis had lower Inverse Simpson scores, although this was not statistically significant (p=0.145). We did not observe taxonomic or compositional differences between patients that experienced immune-mediated adverse events compared to those that did not. Interestingly, patients who relapsed during the first year after surgery had lower Inverse Simpson Scores following one cycle of ICB (p=0.039). In contrast, patients who did not relapse during the first year had a higher relative abundance of Ruminococcus at baseline (p=0.011).ConclusionsThis study strongly suggests an impact of the fecal microbiome on toxicity and relapse in STS patients treated with ICB which can be further explored with larger cohorts.Clinical trial identificationNCT03307616.Legal entity responsible for the studyMD Anderson Cancer Center.FundingMD Anderson Cancer Center.DisclosureAll authors have declared no conflicts of interest. BackgroundThe fecal microbiome is associated with toxicity and efficacy of ICB in multiple malignancies, although little is known about its role in STS. We examined the impact of the fecal microbiome on toxicity and early relapse in a phase II trial of neoadjuvant ICB for extremity/truncal undifferentiated pleomorphic sarcoma (UPS) and retroperitoneal dedifferentiated liposarcoma (DDLPS). The fecal microbiome is associated with toxicity and efficacy of ICB in multiple malignancies, although little is known about its role in STS. We examined the impact of the fecal microbiome on toxicity and early relapse in a phase II trial of neoadjuvant ICB for extremity/truncal undifferentiated pleomorphic sarcoma (UPS) and retroperitoneal dedifferentiated liposarcoma (DDLPS). MethodsPatients (DDLPS, n=17; UPS, n=10) were randomized to receive neoadjuvant nivolumab or nivolumab/ipilimumab, with UPS patients receiving ICB/radiation therapy concurrently. Fecal samples were collected at baseline, after 1 cycle of ICB, and at surgery. Fecal microbiomes were profiled via 16S rRNA gene sequencing and operational taxonomic units determined with UPARSE and the SILVA database. Comparisons were made using alpha and beta diversity scores and taxonomic relative abundances to evaluate differences between the two sarcoma types, patients with early or late relapse, and for those with immune-mediated toxicity, carried out with non-parametric statistical tests. Patients (DDLPS, n=17; UPS, n=10) were randomized to receive neoadjuvant nivolumab or nivolumab/ipilimumab, with UPS patients receiving ICB/radiation therapy concurrently. Fecal samples were collected at baseline, after 1 cycle of ICB, and at surgery. Fecal microbiomes were profiled via 16S rRNA gene sequencing and operational taxonomic units determined with UPARSE and the SILVA database. Comparisons were made using alpha and beta diversity scores and taxonomic relative abundances to evaluate differences between the two sarcoma types, patients with early or late relapse, and for those with immune-mediated toxicity, carried out with non-parametric statistical tests. ResultsFecal microbiomes from DDLPS and UPS patients were found to have similar diversity, composition, and structure at baseline (p=0.431). Fecal microbiomes from both histotypes were characterized by an abundance of Bacteroides sp. and Blautia sp; however, baseline samples from patients with UPS had a higher relative abundance of Faecalibaterium sp. when compared to DDLPS (7.5% vs. 4.7%; p=0.038). Patients that experienced immune-mediated diarrhea or colitis had lower Inverse Simpson scores, although this was not statistically significant (p=0.145). We did not observe taxonomic or compositional differences between patients that experienced immune-mediated adverse events compared to those that did not. Interestingly, patients who relapsed during the first year after surgery had lower Inverse Simpson Scores following one cycle of ICB (p=0.039). In contrast, patients who did not relapse during the first year had a higher relative abundance of Ruminococcus at baseline (p=0.011). Fecal microbiomes from DDLPS and UPS patients were found to have similar diversity, composition, and structure at baseline (p=0.431). Fecal microbiomes from both histotypes were characterized by an abundance of Bacteroides sp. and Blautia sp; however, baseline samples from patients with UPS had a higher relative abundance of Faecalibaterium sp. when compared to DDLPS (7.5% vs. 4.7%; p=0.038). Patients that experienced immune-mediated diarrhea or colitis had lower Inverse Simpson scores, although this was not statistically significant (p=0.145). We did not observe taxonomic or compositional differences between patients that experienced immune-mediated adverse events compared to those that did not. Interestingly, patients who relapsed during the first year after surgery had lower Inverse Simpson Scores following one cycle of ICB (p=0.039). In contrast, patients who did not relapse during the first year had a higher relative abundance of Ruminococcus at baseline (p=0.011). ConclusionsThis study strongly suggests an impact of the fecal microbiome on toxicity and relapse in STS patients treated with ICB which can be further explored with larger cohorts. This study strongly suggests an impact of the fecal microbiome on toxicity and relapse in STS patients treated with ICB which can be further explored with larger cohorts.