Gut Microbiome Composition Is Associated With Response to CD38 Antibody (Daratumumab) Treatment Among Relapsed Multiple Myeloma Patients

INTRODUCTION: Growing data support interactions between host-gut microbes and treatment responses in multiple myeloma (MM), where a higher abundance of Eubacterium hallii in stool samples has been found among MM patients with negative minimal residual disease after induction therapy. Here, we evaluated changes in the gut microbiome associated with daratumumab (dara) based therapy in 40 MM patients, before and after therapy. PATIENTS AND METHODS: Patients with relapsed MM and prior autologous transplantation who had received 1 to 4 prior lines of therapy were eligible. Two stool samples were collected, one within 1 week prior to dara (predara) and one immediately after 4 doses of dara (postdara). Metagenomics sequencing was conducted. Microbiome taxonomic analyses were performed using MetaPhlAn4, and microbial functional pathway analyses were conducted using HUMAnN3.6. QIIME2 was used for compositional and statistical analyses. RESULTS: Of 40 participants enrolled, there were 5 nonresponders; 35 patients achieved partial response (PR) or better (responders). Among responders, 10 patients achieved complete remission (CR), and 25 patients achieved either very good partial response (VGPR) or PR. There were no statistically significant differences between overall pre and postdara gut microbiomes. Differential abundance analysis (ANCOM-BC) showed statistically significant (q ≤ 0.05) overgrowth of Alistipes finegoldii and Acidaminococcus intestini species in responders and Ruminococcus torques, Sellimonas intestinalis and Clostridium symbiosum in nonresponders. Compared to non-CR, CR samples showed enrichment of Faecalibacterium prausnitzii; non-CR samples were enriched in Segatella copri and Faecalimonas umbilicata. DISCUSSION/CONCLUSION: Our results suggest differences in species between clinical responders and nonresponders, but larger prospective studies are needed to confirm these results.