The gut microbiome in multiple myeloma: from disease evolution to therapeutic modulation

Abstract

The therapeutic landscape of Multiple Myeloma (MM), the second most common haematological malignancy, has undergone a paradigm shift with the introduction of anti-CD38 targeting monoclonal antibodies, immunomodulatory drugs and B-cell maturation antigen (BCMA) targeting Chimeric Antigen Receptor (CAR)-T cell therapies, into clinical practice. Increasing evidence indicates that MM disease progression is accompanied by significant alterations in Gut Microbiome (GM) composition and its associated metabolites. Furthermore, emerging studies suggest that the efficacy of commonly used therapeutics, such as bortezomib (BTZ), as well as novel immunotherapies is significantly influenced by the composition and metabolite production of the GM. In this review, we summarize current knowledge on the role of the microbiome in MM pathogenesis and examine how widely used MM therapeutics affect the GM. We further explore how microbial composition modulates clinical outcomes of MM treatments and assess the potential of GM-targeted strategies to improve therapeutic efficacy. Finally, we discuss the key challenges in microbiome research in MM and propose approaches to address them.