Gut Faecalibacterium abundance in patients with plasma cell disorders is associated with survival after autologous HSCT Open Access

• Lower Faecalibacterium abundance was associated with inferior progression free survival.

• Higher gut microbiota alpha diversity and Faecalibacterium abundance were associated with fewer HSCT-induced toxicities.

The gut microbiota (GM) has been linked to the development, progression, and response to therapy in plasma cell neoplasms (PCN). The primary goal of this study was to investigate the relationship between the composition of the GM before and during autologous hematopoietic stem cell transplant (HSCT) with clinical outcomes of patients with PCN. We focused on the genus Faecalibacterium, which includes the most abundant anaerobic commensal bacterium in the GM. Fecal samples were collected prospectively at pre-, mid- (at 1 week from the start of intervention), and end- (at engraftment) intervention (liberalized versus neutropenic diet) and subjected to 16S rDNA sequencing. Eighty-three patients were enrolled. Their median age was 64 (range, 31-79) years. Fifty-four patients were transplanted as part of frontline therapy and 29 for relapsed/refractory disease. With median follow up time for survivors (n= 82) of 32 (range, 0.7-61) months, the median progression free survival (PFS) was 40 months. Higher pre-intervention Faecalibacterium abundance was associated with improved PFS (hazard ratio (HR) = 0.92, 95% confidence interval (CI) 0.86-0.99, p= 0.02). Faecalibacterium abundance was found to decrease early after transplant (p< 0.01). While the administration of high dose melphalan (200 mg/m²) was significantly associated with PFS in both univariable (HR= 0.38, 95% CI 0.19-0.75, p= 0.006) and multivariable (HR= 0.42, 95% CI 0.20-0.87, p= 0.02) analyses, pre-intervention Faecalibacterium abundance remained independently associated with PFS (HR= 0.93, 95% CI 0.86-0.99, p= 0.04) on multivariable analysis. In conclusion, lower pre-intervention Faecalibacterium abundance was associated with inferior PFS.