Influence of the Gut Microbiome on Clinical Outcomes in the CPIT-001 Trial, a Phase Ib-IIA Study of Combined Checkpoint Inhibition with Nivolumab and Ipilimumab after Autologous Hematopoietic Stem Cell Transplantation in Patients at High-Risk for Post-Transplant Recurrence

Background: Autologous stem cell transplantation (ASCT) remains a standard of care for patients with high-risk and recurrent diffuse large B cell lymphoma (DCLBL), T cell lymphoma (TCL) and multiple myeloma (MM). The discovery that differences in the composition of the gut microbiome contribute to the heterogeneity of response to chemotherapies or immunotherapies has prompted us to investigate the influence of the gut microbiome on progression-free survival (PFS) and overall survival in these patient populations treated with combined nivolumab (Nivo) and ipilimumab (Ipi) in the post-ASCT consolidation setting. Methods: Longitudinal analysis of the gut microbiome was performed on stool samples collected from 26 patients (6 de novo DLBCL, 5 recurrent DLBCL, 1 de novo high-risk T cell lymphoma 2 recurrent TCL, 7 transplant-naïve high-risk MM, 4 recurrent MM) treated with Nivo + Ipi, 14-28 days post-ASCT. Stool samples were collected from patients prior to conditioning and ASCT (baseline) and at engraftment (within 72 hrs of absolute neutrophil count ≥ 500/mcL). Stool samples were then collected serially on Weeks 1, 4, 7, 12, 18 and 26 of treatment, 9, 12 and 18 months post-ASCT and at relapse of disease. The composition of the gut microbiome was identified using 16S rRNA sequencing of the V4 amplicon and bioinformatic analysis of α- and β-diversity metrics was performed using the Second Genome Microbiome Discovery Platform. Patients were classified as early relapsers, (n=5), PFS