Metabolic alterations in multiple myeloma and extramedullary disease- a novel niche of therapeutic targets.

Metabolic reprogramming is a hallmark of cancer, actively contributing to tumour growth and therapeutic resistance. Multiple myeloma (MM) is a common haematological malignancy that exhibits distinct metabolic features, while Extramedullary Myeloma Disease (EMD) is a rare but highly aggressive manifestation of MM with increasing incidence, and an elusive metabolic landscape. Shifts in the population dietary habits have reshaped the gut microbiome, potentially altering the host metabolism and driving cancer progression, including MM and EMD. In this review, we examine the three major metabolic pathways in MM and explore emerging evidence linking gut microbiome dynamics to MM and EMD disease progression. Furthermore, we consider recent studies identifying obesity as a MM risk factor and we explore emerging metabolic targets of MM and EMD. By integrating perspectives from metabolic reprogramming, microbiome dynamics, and obesity-related risk, we aim to provide novel perspectives on MM progression from its asymptomatic precursor stage to high-risk EMD.