Identification of Risk Factors for Myeloma Progression in African American Patients
Authors: Mery David E. , Zhan Yihao , Peng Hongling , Siegel Eric , Ashby Cody , Bailey Clyde , Ma Catherine , Xu Hongwei , Al Hadidi Samer , Schinke Carolina , Zangari Maurizio , Thanendrarajan Sharmilan , van Rhee Frits , Tricot Guido , Shaughnessy, Jr John D , Zhan Fenghuang 
Published: December 2024

Background: African Americans (AA) represent 14% of the population of United States, yet they disproportionally represent 20% of all cases of multiple myeloma (MM). MM is a difficult to treat cancer of the plasma cells and the most frequent hematological malignancy among people of African American (AA) descent. Therefore, it represents a critical area of focus regarding remediation of racial disparities in medicine. The Myeloma Center at the University of Arkansas for Medical Sciences (UAMS) has access to long-term follow-up data on over 10,000 patients with MM and related disorders. We have conducted an initial analysis to identify differences in clinical risk factors between baseline MM clinical samples of African Americans (AA) compared to Caucasian Americans (CA).

Materials and Methods: Between 1980 and 2024, baseline clinical data has been obtained on 8099 MM patients admitted at UAMS. This cohort represents 999 (12%) patients of AA descent and 6822 (84%) CA patients. A chi-squared test was used to identify clinical risk factors disproportionately represented in AA compared to CA. We compared risk factors generated from gene expression profiles of newly diagnosed MM patients, treated on total therapy protocols, from 208 AA and 1428 CA. Cox proportional hazard regression analysis was performed separately for AA and CA patient groups identify how risk factors were related to Event Free Survival (EFS) and Overall Survival (OS) in terms of racial/ethnic differences.

Results: We identified significant racial/ethnic differences in MM disease characteristics and other clinical parameters. CA patients were older when first diagnosed with MM (34% ≥ 65 years) compared to AA patients (28% ≥ 65 years). The AA group consisted of significantly more women [532/999 (53%), P &lt; 0.0001] than the CA group [2658/6822 (39%)], which supports reports in the literature that incidence is increasing in black women but approaching stabilization in black men. Our data showed that AA have significantly inferior EFS [hazard ratio (HR) 1.11, P = 0.0156] to CA, but OS was not as clear (HR 1.08, P = 0.0775), possibly due to AA women, overrepresented in our cohort, who have superior survival compared to AA men (HR 0.778, P = 0.0017).

Several clinical MM parameters associated with increased disease severity were overrepresented in AA patients, such as LDH ≥ 190 U/L (35% AA, 27% CA, P = 0.0015), CRP ≥ 4 mg/L (91% AA, 83% CA, P = 0.001), serum ALB &lt; 3.5 (49% AA, 40% CA, P = 0.001), and PLT &lt;150 (21% AA, 18% CA, P = 0.05). Within the AA group, Inferior survival was seen for every parameter except CRP: LDH [OS: HR 1.63, P = 0.0004; EFS: HR 1.51, P = 0.0011], ALB [OS: HR 1.33, P = 0.0017; EFS: HR 1.33, P = 0.0177] and PLT [OS: HR 1.85, P = 1.18e-05; EFS: HR 1.56, P = 0.0009]. Absolute lymphocyte count/absolute monocyte count (ALC/AMC) ≥ 3.6 (48% AA, 40% CA, P = 0.0037) was disproportionately present in AA, but led to improved survival [OS: HR 0.739, P = 0.0301; EFS: HR 0.744, P = 0.0218]. Interestingly, IgG heavy chain MM was overrepresented in AA (64% AA, 56% CA, P= 4.0E-07), while IgA heavy chain (17% AA, 20% CA, P= 0.0318) and free light chain MM (12% AA, 17% CA, P = 0.0002) were overrepresented in CA. IgA MM has been reported to have lower long-term survival rates than IgG MM, but our study only shows this in CA patients [OS: HR 1.21, P = 2.47e-07; EFS: HR 1.19, P = 5.58e-07]. Strikingly, Free Light Chain MM patients only show inferior survival in AA patients [OS: HR 1.27, P = 0.05; EFS: HR 1.42, P = 0.00216].

AA did not show significant differences at the GEP subtype level, GEP70 risk level, or the chromosome level, except in gain of Chromosome 7 (43% AA, 31% CA, 0.0234) and Chromosome 13q deletion (28% AA, 35% CAU, P = 0.0343). For general clinical parameters, AA had disproportionately poor levels, such as high BMI &gt; 30 (44% AA, 31% CA, P = 3.6E-05), Glucose &gt; 200 (4% AA, 2% CA, P = 0.019), and BP systolic&gt;140 (42% AA, 33% CA, P = 0.0021) and BP diastolic &gt; 90 (13% AA, 8% CA, P = 0.0143). Importantly, these parameters were not significant in terms of inferior survival.

Conclusions: Our findings highlight the need for future analyses to determine how racial/ethnic differences effect the survival outcomes for AA and other minority groups compared to studies that are largely overrepresented by CA patients. This study attempts to establish an initial, large clinical analysis of differences in risk factors between AA and CA patients in order to improve treatments for underrepresented racial and ethnic groups in medicine.