It is worth the weight: obesity and the transition from monoclonalgammopathy of undetermined signifi-cance to multiple myeloma

Q: Why are observational studies on obesity and MGUS sometimes conflicting?

Confounding factors, particularly socioeconomic status-related diet quality and adjustment effects in analyses, can lead to heterogeneous results and ambiguous interpretations.

Sep 24, 2026

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The review examines how obesity influences the risk of multiple myeloma (MM) and its precursor, monoclonal gammopathy of undetermined significance (MGUS). It highlights that obesity affects a large proportion of adults globally and is linked to chronic diseases, while MM is driven by uncontrolled plasma-cell clonal expansion. The article summarizes epidemiologic findings on obesity’s association with MGUS and MM, explores biological mechanisms underlying disease progression, and outlines obesity-targeted pharmacologic and lifestyle interventions that may reduce transition risk from MGUS to MM.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

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Introduction

Epidemiologic studies

Obesity as a risk factor for the development of MGUS

Obesity as a risk factor for the progression of MGUS

REVIEW ARTICLE It is worth the weight: obesity and the transition from monoclonalgammopathy of undetermined signiﬁcance to multiple myeloma Ruth Choa,* Cristina Panaroni,* Roma Bhatia, and Noopur Raje Center for Multiple Myeloma, Massachusetts General Hospital, Boston, MA The overweight/obesity epidemic is a serious public health concern that affects >40% of adults globally and increases the risk of numerous chronic diseases, such as type 2 diabetes, heart disease, and various cancers. Multiple myeloma (MM) is a lymphohematopoietic cancer caused by the uncontrolled clonal expansion of plasma cells. Recent studies have shown that obesity is a risk factor not only for MM but also monoclonal gammopathy of undetermined signiﬁcance (MGUS), a precursor disease state of MM. Furthermore, obesity may promote the transition from MGUS to MM. Thus, in this review, we summarize the epidemiological evidence regarding the role of obesity in MM and MGUS, discuss the biologic mechanisms that drive these disease processes, and detail the obesity-targeted pharmacologic and lifestyle interventions that may reduce the risk of progression from MGUS to MM. Introduction Multiple myeloma (MM) accounts for 2% of all cancer cases and 15% of all lymphohematopoietic cancers in the United States.1 It is characterized by elevated serum monoclonal protein and associated CRAB features (hypercalcemia, renal insufﬁciency, anemia, and bony lesions) . Incidence increases with age, is highest in those aged >40 years, and appears to be higher in men and African Americans.1 Other risk factors postulated to be involved in the development of MM include exposure to benzene2 and pesticides,3 obesity,4-9 and genetic factors.10-12 In many cases, monoclonal gammopathy of undetermined signiﬁcance (MGUS) precedes MM and, compared with MM, is characterized by a lower serum level of monoclonal protein (<3 g/dL), bone marrow (BM) clonal plasma cells <10%, lack of CRAB features, and absence of other B-cell proliferative disorders.13 MGUS occurs in 3% of people aged ≥50 years and in 5% of those aged ≥ 70 years.14 It is characterized by 2 major subtypes: (1) immunoglobulin M (IgM) MGUS, which arises from CD30+ lymphoplasmacytic cells (15%), and (2) non-IgM MGUS, which arises from mature plasma B cells (85%) . Non-IgM MGUS poses a higher risk of transformation to MM, 15 and the overall rate of progression from MGUS to MM is ~1% per year, regardless of the duration of follow-up.16 The prevalence of MGUS is higher in men and African Americans, which may be partially attributable to the higher rates of MM observed in this population.17 Obesity is an evergrowing global problem that affects >40% of adults and signiﬁcantly increases the risk of chronic diseases such as type 2 diabetes, heart disease, and cancer.4,18-22 Obesity has been increasingly found to be associated with the development of both MGUS and MM, and recent evidence suggests that it may further promote the transition from MGUS to MM.21 , 23 , 24 Submitted 1 June 2023; accepted 5 July 2023; prepublished online on Blood Advances First Edition 26 July 2023. [https://doi.org/10.1182/](https://doi.org/10.1182/)[ ](https://doi.org/10.1182/)[bloodadvances.2023010822](bloodadvances.2023010822.)[.](bloodadvances.2023010822.) *R.C. and C.P. contributed equally to this work. © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4 . 0 International (CC BY-NC-ND 4 . 0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. 5510 26 SEPTEMBER 2023 • VOLUME 7, NUMBER 18 Consequently, the purpose of this review is threefold: (1) review the literature and describe the current evidence regarding the role of obesity in promoting the transition from MGUS to MM; (2) discuss the biologic mechanisms that may be implicated in driving this association; and (3) detail how this association could be leveraged clinically, wit

FAQs

What role does obesity play in the progression from MGUS to multiple myeloma?

Recent evidence suggests obesity is a risk factor for MM and may promote the transition from MGUS to MM, supporting a progression risk association beyond the baseline MGUS state.

How does MGUS differ from multiple myeloma?

MGUS typically shows lower serum monoclonal protein (<3 g/dL), fewer clonal plasma cells (<10%), lacks CRAB features, and does not involve other B-cell proliferative disorders.

Why are observational studies on obesity and MGUS sometimes conflicting?

Confounding factors, particularly socioeconomic status-related diet quality and adjustment effects in analyses, can lead to heterogeneous results and ambiguous interpretations.

Sep 24, 2026

Uploaded by Cipher