To our knowledge, this was the first epidemiological study to comprehensively describe trends and disparities in MM incidence and mortality over the past two decades. We found that MM incidence rates rose slightly over this period, while MM mortality steadily decreased from 1999–2020. However, substantial disparities were apparent, wherein non-Hispanic Black populations consistently exhibited the highest incidence and mortality of MM, which persisted across strata defined by age, tumor stage at diagnosis, US census region, and urbanization status. Further, we report that non-Hispanic AIAN and AAPI individuals exhibited the lowest MM incidence and mortality rates. Men exhibited the highest MM incidence and mortality rates, highlighting gender disparities. Overall, these disparities highlight the significant burden of MM on patients and the healthcare system, underscoring the need for targeted interventions and screening initiatives for the at-risk populations identified.
Our data aligns with existing literature that non-Hispanic Black Americans exhibit the highest MM incidence and mortality rates [23–25]. These disproportionately higher rates observed among non-Hispanic Black Americans highlight the imperative for further research examining the multifaceted etiology of MM morbidity and mortality, encompassing both genetic predispositions and socio-environmental determinants to inform future targeted intervention strategies.
The higher MM mortality rates that we noted among non-Hispanic Black Americans may be partially influenced by a higher prevalence of MGUS, a precursor lesion to MM, compared to other SIRE groups, potentially explaining the elevated MM incidence rates [26–28]. The risk of progression from MGUS to MM across SIRE groups suggests that the greater incidence of MGUS in certain populations may help explain the higher rates of MM within those groups [26–28]. Specific human leukocyte antigen (HLA) alleles linked to MM susceptibility, coupled with a heightened familial predisposition to MM and related plasma cell dyscrasia, may further contribute to this racial disparity [29–31]. Additionally, structural racism experienced by Black and Hispanic Americans may exacerbate disparities in MM early detection, access to treatment, and outcomes. Prior research demonstrates Black American and Hispanic patients are more likely to experience delays in accessing treatments such as autologous stem cell transplants (ASCT) compared to White patients, hindering their ability to benefit fully from these treatments [32].
Additionally, obesity—an established risk factor for MM and MGUS—disproportionately affects non-Hispanic Black individuals, suggesting a potential pathway through which obesity exacerbates the observed MM disparity [15, 16, 24]. However, while obesity plays a part in every stage of MM progression, the greatest impacts are at the level of precursor disease states like MGUS and SMM [15]. Consequently, targeted screening interventions within high-risk populations, such as those with higher obesity rates, may offer strategic avenues for earlier MM detection and intervention, thus, mitigating the burden of MM within these communities. Broader socioeconomic and structural inequalities also contribute to SIRE disparities in MM incidence and mortality. Structural barriers, including lower median incomes and higher unemployment rates among non-Hispanic Black populations, limit access to quality healthcare and novel treatments, which may contribute to variations in survival outcomes among MM patients [7, 8, 24, 25]. Socioeconomic status may influence other upstream social factors such as education, income, and access to health insurance, all crucial for managing MM, particularly given the substantial financial burden and distress associated with its management [24, 25].
Moreover, prior research demonstrates that health literacy rates may influence the management and outcomes of MM, as higher rates have been documented to reduce emergency department visits, improve survivorship care, and help maintain or improve quality of life among MM survivors [34, 35]. The discrepancy in MM mortality rates among on-Hispanic Black individuals may potentially be explained in part by health literacy challenges; even among those with adequate understanding of MM, access to care remains a complex issue, particularly for costly therapeutic strategies such as ASCT [32–35]. Prior research shows that non-Hispanic Black patients are not only less likely to undergo ASCT but also tend to initiate ASCT later in the disease course, leading to a longer interval from diagnosis to the initiation of novel therapy compared to their non-Hispanic White counterparts [35].
The overall decline in MM mortality rates over the past two decades, consistent with prior research [8], is encouraging. The decline in mortality rates aligns with the introduction of novel therapeutic agents boasting higher efficacy profiles and reduced toxicity, which are shown to be particularly beneficial for elderly MM patients ineligible for ASCT [36, 37]. Further, advancements in ASCT have also led to improved MM prognosis and survival [37, 38]. Immune-based therapies have also contributed to significant improvements in the MM treatment efficacy across diverse patient cohorts [39]. For instance, anti-CD38 monoclonal antibodies, such as daratumumab, as well as other novel MM therapeutics—including bortezomib, lenalidomide, and dexamethasone—have demonstrated prolonged median progression-free survival of 41 months compared to the 8.5 months for control cohorts [39].
Despite these advancements, routine screening for MM is not currently a part of public health interventions and needs to be prioritized for high-risk subgroups. For instance, targeted studies such as iStopMM and PROMISE have investigated the benefits of screening in high-risk populations based on a wide array of sociodemographic factors—such as age, race, family history (e.g., African ancestry), and genetic markers—to identify at-risk individuals with MM precursor conditions such as MGUS or smoldering myeloma, and thereby improve early diagnosis and treatment [41, 41]. In addition to sociodemographic factors, cytogenetic abnormalities such as del(17p), t(4;14), t(14;16), and gain(1q) can also be used to identify patients with high-risk disease at the time of diagnosis [42]. Implementing screening protocols, particularly in regions marked by heightened MM vulnerability and prevalent risk factors, is crucial for addressing the urgent need for early detection and intervention strategies concerning MM within marginalized communities and populations.
Additionally, our findings also indicate that AAPI populations exhibit the lowest rates of MM incidence and mortality compared to other ethnicities, corroborating with prior research [7, 32, 35]. Historically, AAPI populations have shown superior overall survival rates alongside low incidence rates in comparison to non-Hispanic white populations, as documented by several studies [7, 32, 35]. Factors contributing to this trend may include genetic polymorphisms, such as the NQO1*2/*2 polymorphisms observed in Koreans, as well as higher socioeconomic status among AAPI populations [7, 32, 35]
The limited incidence and reporting of MM within AAPI populations may complicate future studies, particularly those aiming to disaggregate MM incidence and mortality within specific subgroups. To our knowledge, there have been no studies to date examining MM incidence and mortality amongst AAPI subgroups, warranting further in-depth investigation in relation to documented risk factors in AAPI communities such as linguistic and health literacy challenges, limited primary care physician visits, low screening rates, and more [45].
We also observed substantial variability in age-adjusted incidence and mortality data for MM among non-Hispanic AIAN/PRCDA populations, which may be attributed to significant data suppression (due to small sample sizes) within the SEER and CDC Wonder databases. This likely results from various social and statistical factors, including the chronic underfunding of Indian Health Services (IHS) and tribal healthcare facilities, leading to insufficient cancer screening services [44]. The displacement of AIAN populations to rural areas by citizenry and US military further compounds limited healthcare access and late-stage disease detection, particularly in MM, posing challenges for obtaining essential incidence and mortality data [45]. Despite attempts to address racial misclassification by linking data to IHS patient registration, substantial misclassification of AIAN individuals persists, likely leading to an underestimation of the cancer burden [46, 47]. Even with efforts to mitigate misclassification, these challenges, coupled with the rarity of MM and limited screening opportunities restricted to PRCDA counties, contribute to significant data suppression, hindering accurate analysis of incidence and mortality rates among AIAN populations [46, 47]. Overall, the isolated geographic distribution, limited screening opportunities, and racial misclassification collectively limit the comprehensive analysis of AIAN data, and further research is needed to better understand the burden of MM within these communities and unique risk factors.
Geospatial analyses have also revealed regional disparities in age-adjusted MM incidence across the United States, with higher rates in the Southeast, Capital District, and New York and lower rates in the Southwest and West [48]. The spatial clustering of MM likely results from a multifaceted interplay of demographic, genetic, lifestyle, and environmental risk factors. However, our US census region-stratified data has revealed that the highest rates of MM mortality within AANHPI populations are concentrated in Western states while the lowest rates were found in the Midwest and Northeast. The differences may reflect the different compositions of AANHPI populations in different regions of the US. For example, 45% of AAPI individuals are living in Western states, with nearly 30% within California, and only 12% in the Midwest and 19% in the Northeast [49].
Our gender-stratified analyses revealed that MM mortality and incidence rates were generally higher among men than women. Our findings are aligned with similar trends found in prior studies and it is substantiated that men are typically 1.5x more likely to develop MM [55]. These findings echo trends observed in prior studies, which consistently show that men are approximately 1.5-fold more likely to develop MM [55]. Independent of factors like age and socioeconomic status, male gender remains a risk factor for MGUS and MM [25]. Gender disparities in MM can be further explained by the increased incidence of MGUS among healthy male populations. The higher incidence of MM in males may also imply that sex plays a role in MM pathogenesis [25], although the underlying mechanisms remain poorly understood, warranting further exploration. One plausible explanation for the higher risk among men is the greater prevalence of hyperdiploidy, characterized by the gain of multiple odd-numbered chromosomes, which is more common in males [51]. Further research is needed to better understand the underlying mechanisms of gender disparities in MM incidence, particularly focusing on the role of sex in MM pathogenesis and genetic factors influenced by gender.
Our study has several limitations. Firstly, due to the cross-sectional study design, we were unable to establish potentially causal relationships between the observed disparities in incidence and mortality and other factors we examined, such as tumor stage and rurality. Secondly, given the comprehensive nature of our paper aimed at providing an overview of incidence and mortality, we relied on ecological-level data from SEER and CDC WONDER, omitting analyses on patient-level characteristics and social determinants of health, such as socioeconomic status, access to health services, health literacy, screening, and comorbidities. Thirdly, we were unable to explore trends in the incidence and mortality of established precursors of MM, such as MGUS or SMM, limiting our ability to understand the impact of early health interventions that diagnose MM precursors and enable early treatment on MM rates. Fourthly, while we included AAPI data as a single aggregate group with relatively lower incidence and mortality rates compared to other SIRE groups, we lacked disaggregated data for AAPI subgroups, hindering our analysis of disparities between these subgroups. Future studies should strive to investigate associations between trends in MM incidence and mortality with social determinants of health and clinical factors to gain deeper insights into the drivers of spatiotemporal changes and disparities.
Despite significant advancements in oncological care and treatment, MM remains a significant burden on the US healthcare system, with increasing incidence over the past two decades. Non-Hispanic Black Americans, in particular, face disproportionately high rates of MM incidence and mortality, underscoring the imperative for equity-centered MM screening and treatments. Understanding SIRE disparities in MM is crucial for guiding public health efforts aiming to improve access to MM detection, treatment, prognosis, survival, and quality of life for patients with MM. Proactive measures—considering social, genetic, and healthcare access factors—are necessary to reduce MM burden, especially within marginalized communities, requiring comprehensive epidemiological surveillance and targeted interventions.