DOES OBESITY PLAY A ROLE IN THE DEVELOPMENT OF MULTIPLE MYELOMA IN PATIENTS WITH MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE: USING DATA FROM THE UNITED STATES VETERANS HEALTH ADMINISTRATION HOSPITAL SYSTEM?

Purpose: Multiple myeloma (MM) is the second most common hematologic malignancy in the United States and is preceded by monoclonal gammopathy of undetermined significance (MGUS). We aimed to investigate the association between obesity and the progression from MGUS to MM.

Methods: Patients with MGUS diagnosed between October 1, 1999 and December 31, 2009 were identified in the U.S. Veterans Health Administration (VHA) database based on the Ninth Revision of the International Classification of Diseases (ICD-9) code 273.1. Unique identifiers of patients were used to link data from the inpatient and outpatient data to the pharmacy data on MM treatment. MM incidence was determined by at least two occurrences of ICD-9 code 203.0 and treatment at any VHA facility within six months of diagnosis. Moreover, two investigators reviewed patient-level clinical data to verify actual diagnosis and date of diagnosis. Interval-censored survival analysis was used, because the time when MM occurs is not directly observed but is known to take place between MGUS and MM diagnoses. Nonparametric maximum likelihood estimator of the survival curves were generated using the expectation-maximization iterative convex minorant algorithm. Multivariate survival analysis, controlling for body mass index (BMI), gender, race, comorbidities, level of creatinine, marital status, and income level, was conducted by parametric accelerated failure time interval-censored analysis with Weibull-modeled survival time. BMI was categorized into normal-weight: 18.5≤BMI<25, overweight: 25≤BMI<30, and obese: BMI>30.

Results: Our sample comprised 9,430 MGUS patients. Among them, 509 patients (5.3%) progressed to MM. Survival curves show the patterns of transformation from MGUS to MM by BMI groups (Figure). In the multivariate analysis, overweight (HR: 1.48; 95% CI: 1.17-1.88) and obese (HR: 1.70; 95% CI: 1.32-2.19) patients were associated with an increased risk of transformation from MGUS to MM. Black race had a higher risk of progression (HR: 1.92; 95% CI: 1.58-2.35). Patients with higher creatinine level (HR: 0.74; 95% CI: 0.59-0.93) and higher Charlson comorbidity index (HR: 0.94; 95% CI: 0.92-0.98) were less likely to develop MM.

Conclusions: This study provides evidence suggesting that overweight or obesity was associated with an elevated risk of transformation from MGUS to MM. As obesity is the only modifiable risk factor for this transformation, we suggest that clinical practice recommend weight loss to people with higher risks of developing MGUS or MM.