Introduction: Emerging studies in MM have shown the association of gut microbiota in MM disease progression, disease response, and treatment toxicity. However, all of the previously conducted work has been done in younger patients with either a precursor condition of MM or those undergoing autologous stem cell transplant. There are no studies of gut microbiota in older transplant ineligible MM patients, which form the majority of patients with MM. The role of gut microbiome may be even more important in older adults with MM, who may have increased gut permeability leading to systemic inflammation and immune dysregulation, altering the gut microbiome and ultimately contributing to poor health outcomes seen in this patient population.
The objective of our study was to characterize the gut microbiome among older adults with MM initiating treatment with dara-len-dex. Our hypothesis was that gut microbiome would be different among frail versus fit older adults initiating treatment.
Methods: Patients with MM who started dara-len-dex were enrolled between January 2023-January 2024. Baseline demographics including frailty status (both IMWG and simplified frailty indices) and disease characteristics were collected in addition to feces samples. DNA was extracted from 23 fecal samples and subjected to 16S rRNA v3-v4 sequencing. We assessed taxonomic diversity through the Shannon and Simpson diversity indices and evaluated beta-diversity using Bray-Curtis dissimilarity. To examine the influence of baseline demographics and disease characteristics on the gut microbiome, we employed Multiple Factor Analysis (MFA), a multivariate method integrating structured groups of variables. This analysis encompassed 20,148 quantitative and qualitative variables organized into 21 variable groups. Multidimensional distance calculations between samples were performed, incorporating taxonomic data, diversity indices, frailty status, disease information, sex, antibiotic and dexamethasone usage, circulating cytokine levels, and various blood markers.
Results: Results revealed no difference in alpha or beta diversity of the gut microbiome based on sex, frailty status ,antibiotic or dexamethasone usage; however, samples clustering based on frailty status (both IMWG and simplified) and dexamethasone use. Frailty status had the largest impact on community composition, with fit and frail patients forming two distinct clusters. The presence of these clear clusters highlight the significant impact of frailty status and dexamethasone usage on the gut microbiome of patients and their associated variables. No differences were detected based on sex and disease cytogenetics at diagnostics.
Conclusions: The results of this study suggests that the gut microbiome of patients with MM initiating treatment with dara-len-dex is notably influenced by the frailty status of the patients. Further follow up is ongoing to understand the impact of this frailty-microbiome association on both toxicity and disease progression in MM.
