Racial Differences in Metabolic Changes during Induction Therapy for Newly Diagnosed Myeloma

Background

Multiple myeloma (MM) disproportionately affects Black populations when compared to White populations. Additionally, metabolic disorders such as obesity and diabetes mellitus have been associated with worse survival in MM based on our prior research. These metabolic disorders also disproportionately affect Black individuals. The goal of this study is to evaluate baseline differences and changes during induction in body mass index (BMI), insulin resistance (adiponectin to leptin (AL) ratio), C reactive protein (CRP), body composition (visceral and subcutaneous adiposity), progression free (PFS) and overall (OS) survival in Blacks compared to White patients. A high AL ratio is associated with better insulin sensitivity.

Method

A total of 389 newly diagnosed MM patients treated with either carfilzomib, lenalidomide and dexamethasone (KRd, N=191) or bortezomib, lenalidomide, and dexamethasone (VRd, N=198) were included. Clinical data on BMI, CRP, age, race, and gender were extracted from electronic health records. The cohort included 51 Black and 280 White patients. Body mass index (BMI) was classified into underweight (BMI < 18.5), normal weight (BMI 18.5- 24.9), and overweight/obese (BMI ≥25). Changes in BMI were grouped as weight stable (BMI < 5% change), weight loss (BMI decrease ≥5%), and weight gain (BMI increase ≥5%).

AL ratio was analyzed on banked biospecimens (n=128 at baseline and n=57 with post induction paired samples). Body composition (tissue compartment volumes for subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and muscle tissue (MT)) was analyzed (n=66 at baseline and n=32 post induction) Wilcoxon rank sum test assessed associations between race and baseline AL ratio and body composition, as well as change during induction. Fisher exact test assessed associations between race and CRP or BMI at baseline and change after induction. Multivariable Cox regression and landmark analyses assessed associations between race and PFS and OS adjusting for gender, age, RISS stage, cytogenetics, and cardiac history, as well as baseline BMI or BMI change.

Results

In this cohort, Black patients were more likely to be female (p=0.02). Post induction, 24.5% Black patients and 17.9% of White patients gained weight, 12.2% Black patients and 16% White patients lost weight, and the rest remained weight stable (p=0.51).

Black patients were more likely to have a low AL ratio at baseline compared to White patients (p=0.006). However, the post induction AL ratio (p=0.30) and change in AL ratio (p=0.76) was not different between groups, possibly due to the smaller number of available samples. An elevated CRP (≥0.5) was seen in significantly more Black patients (43.5%) compared to White patients (25.2%) at baseline (p=0.02). Black patients had significantly higher SAT than white patients at baseline (p = 0.008) and significantly lower VAT (p = 0.014) with no difference in the VAT (p = 0.83) or SAT (p =0.24) change during induction.

In multivariate models including baseline BMI, race was not associated with PFS (p=0.9) or OS (p=0.7). In models including BMI change during induction, race was also not associated with PFS (p=0.5) or OS (p=0.4).

Conclusion

At baseline, Black patients had greater insulin resistance (lower AL ratio), higher inflammation (higher CRP) and higher subcutaneous adipose tissue compared to White patients. These findings highlight the importance of integrating lifestyle interventions such as diet, exercise, and weight management into patient care to address modifiable contributors to racial differences