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Minimal residual disease negativity in multiple myeloma is associated with intestinal microbiota composition

Matthew J. Pianko, Sean M. Devlin, Eric R. Littmann, Aisara Chansakul, Donna Mastey, Meghan Salcedo, Emily Fontana, Lilan Ling, Elizabet Tavitian, John B. Slingerland, Ann E. Slingerland, Annelie Clurman, Antonio L. C. Gomes, Ying Taur, Eric G. Pamer, Jonathan U. Peled, Marcel R. M. van den Brink, Ola Landgren and Alexander M. Lesokhin

Key Points

  • In patients with an MRD treatment response, we found a higher abundance of the butyrate producer E hallii.

  • Deep response to MM therapy is a biomarker for progression-free survival, suggesting association of microbial signature and patient outcome.

Abstract

Patients with multiple myeloma (MM) who achieve minimal residual disease (MRD) negativity after upfront treatment have superior outcomes compared with those who remain MRD+. Recently, associations have been shown between specific commensal microbes and development of plasma cell disorders. Here, we report the association between intestinal microbiota composition and treatment outcome in MM. Microbiota composition of fecal samples collected from 34 MM patients after induction therapy and at the time of flow cytometry–based bone marrow MRD testing was determined by 16S ribosomal RNA sequencing. We observed a higher relative abundance of Eubacterium hallii in the 16 MRD patients relative to the 18 MRD+ patients. No association was observed between microbial relative abundance and autologous stem cell transplantation history or MM paraprotein isotype. No differences in microbiota α diversity were observed between MRD and MRD+ patients. The potential association of microbiota composition with treatment response in MM patients is an important parameter for additional correlative and clinical investigation.

  • Submitted January 25, 2019.
  • Accepted April 17, 2019.
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