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

IF 2.3 4区医学 Q1 MEDICINE, GENERAL & INTERNAL

Journal of the National Medical Association Pub Date : 2025-09-01 DOI:10.1016/j.jnma.2025.08.088

Roshana Brown , Ross Firestone , Ram Prakash Thirugnanasambandam , Sandeep Raj , Andriy Derkach , Tala Shekarkhand , Colin Rueda , Kylee Maclachlan , Malin L. Hultcrantz , Sham Mailankody , Heather Landau , Gunjan Shah , Michael Scordo , Hani Hassoun , Alexander M. Lesokhin , Sergio Giralt , Michael Pollak , Neha Korde , Saad Z. Usmani , Carlyn R. Tan , Urvi A. Shah

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引用次数: 0

Abstract

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

查看原文本刊更多论文

新诊断的骨髓瘤诱导治疗期间代谢变化的种族差异

背景：与白人相比，多发性骨髓瘤（MM）对黑人的影响不成比例。此外，根据我们之前的研究，代谢紊乱如肥胖和糖尿病与MM患者的生存率较差有关。这些代谢紊乱对黑人的影响也不成比例。本研究的目的是评估黑人与白人患者在体重指数（BMI）、胰岛素抵抗（脂联素与瘦素（AL）之比）、C反应蛋白（CRP）、身体成分（内脏和皮下脂肪）、无进展（PFS）和总生存率（OS）诱导过程中的基线差异和变化。高AL比值与更好的胰岛素敏感性相关。方法采用卡非佐米、来那度胺和地塞米松联合治疗（KRd， N=191）或硼替佐米、来那度胺和地塞米松联合治疗（VRd， N=198）的新诊断MM患者389例。从电子健康记录中提取BMI、CRP、年龄、种族和性别的临床数据。该队列包括51名黑人和280名白人患者。体重指数（BMI）分为体重过轻（BMI < 18.5）、体重正常（BMI 18.5 ~ 24.9）和超重/肥胖（BMI≥25）。BMI变化分为体重稳定（BMI变化≥5%）、体重减轻（BMI下降≥5%）和体重增加（BMI增加≥5%）。对储存的生物标本（基线时n=128，诱导后配对标本n=57）进行AL比率分析。分析体组成（皮下脂肪组织（SAT）、内脏脂肪组织（VAT）和肌肉组织（MT）的组织室体积）（基线时n=66，诱导后n=32）。Wilcoxon秩和检验评估种族和基线AL比与体组成之间的关系，以及诱导过程中的变化。Fisher精确试验评估了种族与CRP或BMI在基线和诱导后的变化之间的关系。多变量Cox回归和里程碑分析评估了种族与PFS和OS之间的关系，调整了性别、年龄、RISS分期、细胞遗传学和心脏病史，以及基线BMI或BMI变化。结果在该队列中，黑人患者以女性为主（p=0.02）。入组后，24.5%的黑人患者体重增加，17.9%的白人患者体重增加，12.2%的黑人患者体重减轻，16%的白人患者体重减轻，其余体重保持稳定（p=0.51）。与白人患者相比，黑人患者在基线时AL比更低（p=0.006）。然而，诱导后AL比（p=0.30）和AL比变化（p=0.76）组间没有差异，可能是由于可用样本数量较少。基线时，黑人患者（43.5%）CRP升高（≥0.5）明显多于白人患者（25.2%）（p=0.02）。黑人患者在基线时SAT显著高于白人患者（p = 0.008），VAT显著低于白人患者（p = 0.014），诱导时VAT （p = 0.83）和SAT （p =0.24）变化无差异。在包括基线BMI在内的多变量模型中，种族与PFS （p=0.9）或OS （p=0.7）无关。在诱导过程中包括BMI变化的模型中，种族也与PFS （p=0.5）或OS （p=0.4）无关。在基线时，与白人患者相比，黑人患者有更高的胰岛素抵抗（更低的AL比），更高的炎症（更高的CRP）和更高的皮下脂肪组织。这些发现强调了将生活方式干预（如饮食、运动和体重管理）纳入患者护理的重要性，以解决造成种族差异的可改变因素

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来源期刊

Journal of the National Medical Association 医学-医学：内科

CiteScore

4.80

自引率

3.00%

发文量

139

审稿时长

98 days

期刊介绍： Journal of the National Medical Association, the official journal of the National Medical Association, is a peer-reviewed publication whose purpose is to address medical care disparities of persons of African descent. The Journal of the National Medical Association is focused on specialized clinical research activities related to the health problems of African Americans and other minority groups. Special emphasis is placed on the application of medical science to improve the healthcare of underserved populations both in the United States and abroad. The Journal has the following objectives: (1) to expand the base of original peer-reviewed literature and the quality of that research on the topic of minority health; (2) to provide greater dissemination of this research; (3) to offer appropriate and timely recognition of the significant contributions of physicians who serve these populations; and (4) to promote engagement by member and non-member physicians in the overall goals and objectives of the National Medical Association.