Gut Microbiome Associated With Minimal Residual Disease Negativity in Multiple Myeloma

The gut microbiome has received increased attention for its connection to various aspects of health, and now a new study indicates that microbiota composition in the gut could have implications for treatment response in multiple myeloma (MM).

Among 34 patients with MM who completed induction therapy, a higher abundance of Eubacterium hallii was associated with minimal residual disease (MRD) negativity. The researchers observed a higher relative prevalence of the butyrate producer in the 16 patients who were MRD negative compared with the 18 patients who were MRD positive (median, 3.16% vs 1.01%).

“Our results are novel and support the concept that intestinal microbiota composition is associated with deep treatment response,” the researchers wrote.

MRD has become a clinically relevant end point in MM and the development of new therapies for the disease because of its association with patient outcomes. Compared with patients who are MRD positive, patients who are MRD negative have better outcomes.

All patients enrolled in the study between January 2017 and April 2018 had completed first-line therapy and were eligible for lenalidomide maintenance. Prior to initiating lenalidomide, patients were tested for their MRD status using a validated bone marrow—based flow cytometric assay. The researchers determined the prevalence of E hallii and other microbes by performing 16S ribosomal RNA sequencing of fecal samples.

The analysis also showed that Faecalibacterium prausnitzii, a common butyrate-producing commensal microbe often positively associated with human gut health, was more enriched in patients who were MRD negative (1.43% vs 0.003%) and could potentially be associated with MRD-negative status after initial therapy for MM.

“Butyrate is known to inhibit in vitro production of IL-17A via downregulation of Th17 cells in human peripheral blood mononuclear cells,” wrote the researchers. “Of note, IL­-17—producing Th17 cells induced by microbiota have been associated with disease pathogenesis in a murine MM model, and after bone marrow transplantation, promotion of MM immune escape is mediated by donor-derived IL-17A.”

Meanwhile, there was no observed association between microbial relative abundance and autologous stem cell transplantation history or MM paraprotein isotype. There were also no differences in microbiota α diversity observed based on MRD status.

The researchers recommended that future studies validate their findings in larger cohorts and allow for additional characterization of the relationships between disease characteristics versus overall health status in microbial composition in the gut as it relates to treatment response. They added that preclinical studies are warranted to better understand the molecular relationship between microbiome signature and clinical outcomes in MM and other hematologic malignancies.

Reference

Pianko M, Devlin S, Littmann E, et al. Minimal residual disease negativity in multiple myeloma is associated with intestinal micobiota composition [published online July 9, 2019]. Blood Adv. doi: 10.1182/bloodadvances.2019032276.