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Obesity is a concern in the general population, and its influence on people with multiple myeloma (MM) is increasingly recognized to be linked to poorer outcomes. However, the specific impact of visceral fat鈥攁 marker of metabolic dysfunction鈥攐n MM prognosis remains unclear in this patient population. 

A recent study published in JAMA Oncology sheds light on this matter, offering valuable insights for the management of multiple myeloma. Ehsan Malek, MD, and colleagues investigated the impact of visceral obesity on progression of multiple myeloma in patients undergoing hematopoietic cell transplantation (HCT). 

Study design and patient characteristics

The authors conducted a secondary analysis of data from the Phase III STaMINA trial. This large-scale, randomized controlled trial compared three different treatment regimens following hematopoietic cell transplantation in 758 patients diagnosed with multiple myeloma. The participants were divided into 3 groups based on treatment: 

• A second HCT followed by lenalidomide maintenance therapy (n=247)
• Consolidation with lenalidomide/bortezomib/dexamethasone therapy followed by lenalidomide maintenance (n=254)
• Lenalidomide maintenance therapy alone (n=257)

The researchers specifically focused on the impact of visceral obesity, measured by waist-to-hip ratio (WHR), on progression-free survival (PFS) and overall survival (OS) and quality of life (QoL) at baseline, 1-year, 2-year, 3-year, and 4-year time points with a median follow up time of 6 years (range 0.4-8.5). Therefore, only patients with WHR measurements and QoL data were included in the secondary analysis reported in this study (n=549). 

Median age at enrollment was 55.5 years and 17% were African American. A statistically significant difference in the prevalence of high waist-to-hip ratio was observed between White (n=446) and African American (n=103) patients (P=0.026), with a higher proportion of White patients having high WHR. 

Similarly, a significant difference was found between male (n=332) and female (n=217) patients (P=0.001), with males having a higher prevalence of high WHR. Prior to enrollment, 73% of patients received triple-drug antimyeloma initial therapy. Lenalidomide, bortezomib, and dexamethasone (RVD) was the most common initial therapy regimen, used in 55% of patients. Most patients (77%) were considered to have standard risk disease 

Challenging assumptions on the link between obesity and survival

Median WHR was 0.94 (range, 0.52 to 1.86). Contrary to expectations, there was no significant association between WHR and either PFS or OS in patients undergoing hematopoietic cell transplantation. This finding held true after adjusting for potential confounding factors such as age, sex, and disease stage. 

Median body mass index (BMI; 29.11 [range, 17.58 to 69.59]), another common measure of obesity, also failed to predict PFS or OS. Interestingly, the study noted a higher prevalence of high BMI in African American patients compared to White patients, but paradoxically, their WHR was lower (P=0.044). This highlights the limitations of BMI as a sole measure of obesity and underscores the need for more nuanced approaches, especially in diverse populations.

Apart from the Social/Family Well-being subscale of the FACT-G, none of the other QoL measures assessed using validated questionnaires showed significant correlation with WHR, suggesting that visceral obesity may not directly impact patient-reported outcomes in this context.

Limitations and future directions

鈥淥ur finding suggests obesity should not count as an important decision making factor when it comes to HCT eligibility for MM. Hence, data from commonly used comorbidity indices such as Sorror score that includes obesity as important prognostic factor, should not be extrapolated for MM patients,鈥� the authors wrote. 

Furthermore, BMI may not be a reliable indicator of visceral fat distribution for patients with multiple myeloma, particularly in diverse populations. While these factors may not directly impact clinical outcomes or QoL in the context of HCT, the potential long-term health implications, including cardiovascular disease and diabetes, should not be ignored and need further investigation in this patient population. 

Physicians managing MM should consider a comprehensive approach that addresses obesity and its associated comorbidities. By continuing to explore this complex relationship, treatment strategies can be optimized to improve the overall well-being of patients.

The authors acknowledge several limitations in their study, including selection bias. Dr. Malek and his team also noted that the primary objective of the STaMINA trial was not designed specifically to assess the impact of obesity on clinical outcomes in multiple myeloma such those reported in this secondary analysis. 

Due to the relatively short follow-up period, this study may not have captured the full spectrum of long-term outcomes, potentially underestimating the impact of the intervention. Future studies with extended follow-up using imaging techniques to precisely assess visceral fat distribution and its metabolic consequences are warranted to explore the long-term sustainability of these findings.

Published: February 15, 2024