Advisor(s)

Elizabeth Brown

Committee Member(s)

Gayathri Ravi
Vishnu Reddy

Document Type

Thesis

Date of Award

6-18-2026

Degree Name

Master of Science (MS)

School

Joint Health Sciences (Interdisciplinary)

Department

Joint Health Sciences

Abstract

Multiple Myeloma (MM) is the second most common hematologic malignancy in the United States. It is characterized by the accumulation of clonally expanded plasma cells in the bone marrow, which leads to end organ damage and myeloma-defining events requiring treatment. The only modifiable risk factor for MM is obesity. However, associations between obesity, bone marrow adipocytes, and tumor burden at MM diagnosis remain unclear. We evaluated associations of bone marrow adipocytes, body mass index (BMI), and clinical features of tumor burden among 168 patients with histologically confirmed newly diagnosed multiple myeloma (NDMM) enrolled in the Integrative Molecular and Genetic Epidemiology (IMAGE) study between 2009 and 2025 using multivariable linear regression adjusted for confounders, overall and stratified by self-reported race and obesity category. Bone marrow adiposity, quantified using QuPath MarrowQuant 2.0, was strongly and consistently inversely associated with multiple markers of tumor burden at diagnosis, including higher disease stage, adverse cytogenetic risk, greater bone marrow plasma cell infiltration, elevated serum monoclonal protein, increased β2-microglobulin, anemia, renal dysfunction, and hypercalcemia (p ≤ 0.05). In contrast, histologically determined adiposity was not significantly associated with BMI at diagnosis or BMI one-year prior diagnosis in multivariable-adjusted models. The effect of the association of bone marrow adipocytes with clinical features was modified by BMI, with a reduction in the extent of adipocyte depletion observed in patients with obesity. Differences in bone marrow adiposity and tumor burden were observed by race, suggesting differential engagement of the marrow niche. Histologically quantified bone marrow adiposity at diagnosis reflects tumor-driven remodeling of the marrow niche and is strongly associated with disease severity in NDMM. Despite obesity being a risk factor for myeloma, BMI is a poor surrogate for the bone marrow microenvironment in patients with established disease. These findings highlight marrow adiposity as a biologically meaningful marker of tumor burden and warrant further investigation of adipocyte-tumor interactions and differences by race to improve risk stratification and tailored treatments.

Keywords

body mass index;bone marrow adipocyte;multiple myeloma;obesity;tumor burden

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