Impact of body mass index on the prognosis of patients with newly diagnosed Multiple Myeloma Open Access

• Body mass index at the extremes is a poor prognostic factor for newly diagnosed patients with multiple myeloma

• Patients with severe obesity have worse progression-free survival and overall survival

Although obesity is an established modifiable risk factor for multiple myeloma (MM), the influence of obesity on survival among Black patients, for whom obesity and MM are more common, is less clear. We evaluated the association of body mass index (BMI) with progression free survival (PFS) and overall survival (OS) among 834 histologically confirmed cases with newly diagnosed MM (NDMM) enrolled in the Integrative Molecular And Genetic Epidemiology study between 2009 and 2020. We estimated the association of BMI with the risk of progressed disease and all-cause and MM-specific mortality using hazard ratios (HR) and corresponding 95% confidence intervals (CI) calculated from multivariable Cox proportional hazard models adjusted for prognostic factors, overall and stratified by self-reported race and sex. Compared to NDMM patients with normal BMI at diagnosis (18.5-24.9kg/m2), positive associations with all-cause mortality were observed at the extremes of diagnostic BMI with 52% and 147% increased risks of death in patients with underweight (BMI<18.5 kg/m2; HR=1.52, 95% CI 0.48-4.84) and obesity (BMI≥30.0 kg/m2; HR=2.47, 95% CI 1.26-4.85), respectively. Patients with severe obesity (BMI≥35kg/m2) had the highest risk compared to those with a normal BMI (HR=3.14, 95% CI 1.50-6.55), particularly among White (HR=3.22, 95% CI 1.30-7.94) and female (HR=4.17, 95% CI 1.20-14.47) patients with NDMM, albeit the differences by race and sex were not statistically significant (Pinteraction≥0.60). Severe obesity was also significantly associated with an 83% elevated risk of progressed disease among NDMM patients (HR=1.83, 95% CI 1.04-3.24). Findings were similar for MM-specific mortality. These findings highlight the importance of weight management as a potential strategy to improve the prognosis of all patients with NDMM.