Session: 731. Autologous Transplantation: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Biological therapies, adult, Plasma Cell Disorders, Diseases, Therapies, Lymphoid Malignancies, Adverse Events, Biological Processes, microbiome, Study Population, Human, Transplantation
Methods and Results: We serially collected stools samples from 53 MM patients at time of melphalan conditioning (pre-ASCT), engraftment (72hrs of absolute neutrophil count ≥ 500/mcL), and 60-120 days post-ASCT. Taxonomic profiling was performed using 16S rRNA sequencing of the V4-V5 region and amplicon sequence variants (ASV) were annotated against the NCBI 16S database using BLAST. We found lower alpha-diversity at neutrophil engraftment from pre-ASCT, using inverse Simpson diversity index (p=0.0001, Wilcoxon matched pairs signed rank test, n=45). Recovery of diversity to pre-ASCT levels was attained 60-120 days post-ASCT (p=0.001, n=41). However, we did not observe any significant differences in alpha-diversity of patients with ES and without ES at each timepoint tested (Fig.1A). The domination taxa profiles (defined as the relative abundance of a single taxon >30%) differed between patients with and without ES at each timepoint (Fig. 1B). The domination of Enterococcus was only evident in ES patients (pre-ASCT, engraftment) whereas Streptococcus was unique to non-ES patients (engraftment, post-ASCT). Blautia had a higher frequency of domination in non-ES patients compared to ES patients prior to ASCT, during engraftment and post-ASCT. Using Random Forest, a supervised machine-learning algorithm, Streptococcus, Ruminococcus, Coprococcus, and Enterococcus had the highest variable significant features at engraftment.
Conclusions: We found that domination of Enterococcus prior to conditioning and ASCT and further increasing during engraftment is associated with increased risk of ES. Our findings suggest that GM may impact immune-related adverse events and outcomes in MM patients undergoing ASCT and provide the rationale for microbiota-centered interventions.
Disclosures: Feinman: BMS: Honoraria; Takeda: Honoraria; GSK: Honoraria; Janssen: Honoraria; Merck: Other: Consulting; Cellularity: Membership on an entity's Board of Directors or advisory committees. Biran: Amgen, Janssen, Karyopharm, Merck, BMS, Sanofi: Consultancy, Research Funding. Siegel: BMS: Honoraria, Speakers Bureau; COTA: Current equity holder in private company, Current holder of stock options in a privately-held company; GSK: Honoraria, Speakers Bureau; Takeda: Honoraria; Janssen: Honoraria; Merck: Honoraria; Celularity: Membership on an entity's Board of Directors or advisory committees. Peled: Hanson Wade Limited: Other: Speaking; French National Cancer Institute (INCa): Consultancy; HayMatick Meetings & Events: Other: Speaking; University of Nebraska Medical Center: Other: Speaking; William Blair & Company, L.L.C.: Other: Speaking; Parker Institute for Cancer Immunotherapy: Other: Attending a conference , Research Funding; University Hospital Regensburg: Other: Speaking; University of Pennsylvania: Other: Lecture/Speaking; Clinical Immunology Society: Other: Lecture/Speaking; KongresKompagniet A/S: Other: Speaking; apanese Society of Hematology: Other: Speaking; Arjun Pai: Consultancy; Seres Therapeutics: Other: Memorial Sloan Kettering Cancer Center (MSK) has financial interest relative to Seres Therapeutics ; intellectual property applications related to the microbiome: Other: He has filed intellectual property applications related to the microbiome (reference numbers #62/843,849, #62/977,908, and #15/756,845). ; MaaT Pharma: Consultancy; Postbiotics Plus Research: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Consultancy; DaVolterra: Consultancy; Seres Therapeutics: Other: Intellectual Property Fees & Travel Funding , Research Funding.
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