Unraveling Obesity and Multiple Myeloma: Insights from Epidemiology and Molecular Mechanisms

Abstract

Purpose of review: The global incidence of obesity has risen dramatically in recent decades, with consequent detrimental health effects. Extensive studies have demonstrated that obesity significantly affects the risk, prognosis, and progression of various cancers, including multiple myeloma (MM). As an established modifiable risk factor for both MM and its precursor stages -monoclonal gammopathy of unknown significance (MGUS) and smoldering MM (SMM)- the association between obesity and disease onset has become a compelling area of research. This review presents a comprehensive overview of the current epidemiological evidence linking obesity to MM, emphasizing its role in disease pathogenesis and patient outcomes. It also offers insights into the molecular mechanisms underlying this deleterious association, and discusses therapeutic strategies targeting obesity-driven contributions to MM.

Recent findings: Emerging epidemiological evidence suggests that obesity not only influences MM development but also alters its biological behavior, impacting myelomagenesis, and clinical outcomes. Biologically, multiple pathways exist through which adipose tissue may drive MM onset and progression. Obesity fosters a state of chronic inflammation, where dysfunctional adipocytes and fat-infiltrating immune cells release proinflammatory cytokines, growth factors, adipokines, and fatty acids, contributing to the proliferation and expansion of MM. Additionally, communications between MM cells and adipocytes within the bone marrow are crucial in MM biology. Collectively, the discoveries described in this review underscore the necessity for broader preclinical and clinical investigations to better characterize the complex interplay between obesity and MM, and to determine whether lifestyle interventions can impact MM incidence and clinical outcomes, particularly in high-risk populations.

Keywords: Adipokines; Body mass index; Bone marrow microenvironment; Monoclonal gammopathy of unknown significance; Multiple myeloma; Obesity; Smoldering multiple myeloma.

Fig. 1

Mechanisms linking obesity with MM. Obesity is correlated with crucial local and systemic variations, including different releases of cytokines, adipokines (mainly leptin), growth factors and inflammatory molecules. The intricate interplay across all these alterations might support MM development, progression and drug resistance. BMAds: bone marrow adipocytes; DHEA: dehydroepiandrosterone; IGF: insulin-like growth factor; iNKTs: invariant natural killer T cells; IFN-γ: interferon gamma; JAK2: Janus kinase 2; LEPR: leptin receptor; MM: multiple myeloma; STAT3: signal transducer and activator of transcription