Global, Regional, and National Burdens and Trends of Multiple Myeloma in Men Aged 60 Years and Older: An Analysis using the Global Burden of Disease Database (1990-2021)

Global, Regional, and National Burdens and Trends of Multiple Myeloma in Men Aged 60 Years and Older: An Analysis using the Global Burden of Disease Database (1990-2021) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Global, Regional, and National Burdens and Trends of Multiple Myeloma in Men Aged 60 Years and Older: An Analysis using the Global Burden of Disease Database (1990-2021) Hui Sun, Lixiang Yan, Lijun Fang, Yanan Jia, Gengda Zhu, Qin Rao, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8453482/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Multiple Myeloma (MM) is the second most prevalent hematological disease worldwide. In light of rapid advances in medical technologies and complex socioeconomic circumstances, a report detailing the latest epidemiological patterns of MM in men aged ≥ 60 years would be vital for policymakers to ensure judicious healthcare resource use and allocation, forming the basis of this study. Herein, we analyzed data from the Global Burden of Disease (GBD) database (from 1990 to 2021). We specifically focused on four key MM-related indicators, including prevalence, incidence, Disability-Adjusted Life-Years (DALYs), and Estimated Annual Percentage Change (EAPC). The data were largely presented as estimated 95% Uncertainty Intervals (UI). The age-period-cohort (APC) and Average annual percentage change (AAPC) model was used for further analysis. In 2021, the global MM prevalence, incidence, and DALYs in men aged ≥ 60 years were approximately 159,923, 64,181, and 980,993, respectively. Furthermore, over the past 32 years, the global MM prevalence, incidence, and DALY rates have increased, with EAPC values of 1.70 (95% UI: 1.50 ~ 1.90), 0.72 (95% UI: 0.63 ~ 0.82), and 0.22 (95% UI: 0.14 ~ 0.29), respectively. It is also noteworthy that in 2021, among the five Socio-Demographic Index (SDI) regions, the MM prevalence (91,233), incidence (33,288), and DALYs (44,767,678) in men aged ≥ 60 years were the largest number in the high SDI regions, accounting for ⁓50% of the global total. This phenomenon highlights the significance of tailored interventions for MM patients, aligning with several World Health Organization’s (WHO) sustainable development goals. MM Burden of Disease men aged ≥ 60 years DALYs Age-period-cohort analysis GBD 2021 Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction Multiple Myeloma (MM), a hematological tumour characterized by malignant clonal plasma cell proliferation in the bone marrow, remains incurable and is presently the second most prevalent among hematological tumours ( 1 , 2 ). Significant progress has recently been realized in MM treatment, with combination chemotherapy interventions increasingly being employed to clinically prolong MM patients’ survival and improve their Quality of Life (QoL) ( 3 , 4 ). Nonetheless, most MM patients still end up with disease recurrence, a phenomenon partly attributable to the fact that MM is a heterogeneous plasma cell malignant disease. This heterogeneity could be attributed to the different biological characteristics of the patients and is mainly reflected in clinical features and patient survival outcomes ( 5 ). Notably, MM-related morbidity and mortality rates have been established to be particularly higher among men aged ≥ 60 years, with both Age-Standardized Incidence Rate (ASIR) and Age-Standardized Mortality Rate (ASMR) increasing with age. Furthermore, there is a 1.5- to 2-fold gender-specific difference in ASIR and ASMR, with the rates consistently higher in men than in women. Therefore, this study aimed to examine the MM burden in men aged ≥ 60 years ( 6 ). Methods Data sources Herein, global health data (from 1990 to 2021) of male MM patients aged ≥ 60 years was retrieved from the Global Burden of Disease (GBD) database, including global, regional, and national incidence rates and counts, mortality rates and counts, and Disability-Adjusted Life Year (DALY) rates and counts. The above data were integrated using the Bayesian meta-regression tool DisMod-MR2.1, yielding internally consistent morbidity and mortality rates with 95% Uncertainty Intervals (95% UIs)) ( 7 ). Notably, as a measure of disease burden, DALYs comprise two components: Years of Life Lost (YLLs) and Years of Life Lived with Disability (YLDS) ( 8 ). In this study, elderly MM patients aged ≥ 60 years were categorized into eight age groups: 60–64, 65–69, 70–74, 75–79, 80–84, 85–89,90–94, and ≥ 95 years. Furthermore, based on the Socio-Demographic Index (SDI), 204 countries and territories were identified and divided into five categories, ranging from low to high SDI ( 9 , 10 ). For a comprehensive analysis, the global map was further divided into 21 regions based on geographic locations. Statistical methods Linear regression could be useful in estimating trends across various indicators over time in public health and epidemiological studies. However, the actual time series data may be more complex. Therefore, in this study, we determined the Estimated Annual Percentage Change (EAPC) values and their corresponding 95% UIs using linear regression ( 11 , 12 ). Notably, the EAPC values could depict trends in MM prevalence, incidence, and DALY rates ( 13 , 14 ). Herein, both the EAPC value and the lower bound of the 95% Confidence Interval (CI) being > 0 indicated an upward trend in the disease rates among the elderly population. Conversely, both the EAPC value and upper boundary of the 95% CI being < 0 indicated a decreasing trend in the disease rates. The SDI, a composite index often used to assess the level of socio-economic development in a country, was also used in this study as a measure. We determined the correlation coefficients between SDI and both EAPC and the incidence rates, with higher correlation coefficients indicating a closer relationship. Statistical analyses were performed using R software, with multiple R packages used for data processing and visualization. The global burden of MM patients in men aged ≥ 60 years was depicted using a world map, showing the burden of the disease in 204 countries and 21 regions. Results or differences with p < 0.05 were considered statistically significant. Average annual percentage change (AAPC) model was conducted a further assessment. The age-period-cohort (APC) model was used to further examine the effects of age, period, and birth cohort on changes in MM prevalence, incidence, and DALY rates over the past 30 years ( 15 ). Results Global level Globally, the prevalence, incidence, and DALYs of MM in men aged ≥ 60 years have all increased significantly. Specifically, from 1990 to 2021, the MM prevalence, incidence, and DALY cases increased from 41,667 to 159,923, 21,071 to 64,181, and 379,760 to 980993, respectively. Furthermore, from 1990 to 2021, the MM incidence, prevalence, and DALY rates in males aged ≥ 60 years all increased, with EAPC values of 0.72% (95% CI: 0.63 to 0.82), 1.70% (95% CI: 1.50 to 1.90), and 0.22% (95% CI: 0.14 to 0.29), respectively. These findings suggest a general upward trend in the MM burden in men aged ≥ 60 years(Table 1 , Table 2 , Table 3 , Fig. 1 , Fig. 2 ). SDI regional level In 2021, men aged ≥ 60 years had the highest MM prevalence, incidence, and DALY cases. Furthermore, the high SDI region exhibited the highest MM prevalence, incidence, and DALY rates in 2021, accounting for ⁓50% of total global cases. Additionally, from 1990 to 2021, the MM prevalence, incidence, and DALY rates in the Middle SDI region showed a rapid upward trend, with EAPC values of 3.49 (95% CI: 3.35 to 3.62), 2.46 (95% CI:2.31 to 2.62), and 2.03 (95% CI:1.85 to 2.21), respectively(Table 1 , Table 2 , Table 3 , Fig. 1 , Fig. 2 ). GBD regional level Over time, men aged ≥ 60 years demonstrated increases in the MM prevalence, incidence, and DALY rates across all regions. Furthermore, over the past 32 years, increases in the MM prevalence and DALY rates have been observed in most regions, with East Asia and Eastern Europe demonstrating the largest increases, showing EAPC values of 6.14 (95% CI: 5.58 to 6.71) and 2.97 (95% CI: 2.48 to 3.47) for prevalence and 3.47 (95% CI: 2.78 to 4.16) and 1.49 (95% CI: 1.18 to 1.80) for DALY, respectively. Conversely, Oceania showed a decline in both the MM prevalence and DALY rates, with EAPC values of -0.25 (95% CI: -0.34 to -0.16) and − 0.33 (95% CI: -0.41 to -0.25), respectively. Moreover, the MM prevalence and DALY rates among men aged ≥ 60 years from high-income Asia-Pacific and North American regions showed opposite trends, with EAPC values of 0.94 (95% CI: 0.77 to 1.12) and 0.77 (95% CI: 0.52 to 1.03) for prevalence and − 0.83 (95% CI: -0.96 to -0.69) and − 0.71 (95% CI:-0.82 to -0.60) for DALY, respectively. This trend could be attributed to local healthcare standards and economic conditions(Table 1 , Table 2 , Table 3 , Fig. 1 , Fig. 2 ). Country level The MM incidence, prevalence, and DALY rates in men aged ≥ 60 years also varied significantly across the globe by country. For MM incidence, prevalence, and DALY rates, China and the United States had the highest and lowest EAPC values, respectively (Fig. 3 ). Age patterns In 2021, 21 regions recorded the lowest MM prevalence rate among men aged ≥ 95 years, as well as the lowest MM incidence rate among men aged 60–64 years. Oceania had the lowest DALY rate among men aged ≥ 95 years. The MM prevalence, incidence, and death rates among men aged 60–74 years correlated positively with age, but decreased with further increases in age. Similarly, the MM DALY rate in men aged 60–69 years correlated positively with age but decreased with further increases in age (Fig. 4 ). Association between MM burden and SDI In 2021, the MM prevalence, incidence, and DALY rates in men aged ≥ 60 years correlated positively with SDI. With advancements in the global economy, the overall burden of the disease has risen, and the global burden of MM in men aged ≥ 60 years has reached unexpectedly high levels. Across the 21 regions, the burden of MM in men aged ≥ 60 years was relatively stable when SDI values remained between 0.3 and 0.5. However, it peaked when the SDI value reached 0.9, especially among male MM patients aged ≥ 60 years. Regionally, the MM burden was unexpectedly higher in Western Europe and unexpectedly lower in Eastern Europe, Central Asia, and Southeast Asia. Nationally, New Zealand, Canada, and Australia demonstrated higher-than-expected MM burdens in men aged ≥ 60 years, while Yemen, the Gambia, and the United States had lower-than-expected MM burdens (Fig. 5 ). AAPC analysis of the MM prevalence, incidence, and DALY rates The global prevalence rate and incidence rate of AAPC showed an upward trend from 1990 to 2017, and a downward trend after 2017. The AAPC of DALY rate showed an upward trend from 1990 to 2002, a downward trend from 2002 to 2006, and a straight upward trend after 2006 (Fig. 6 ). Age-period-cohort analysis of the MM prevalence, incidence, and DALY rates The MM prevalence, incidence, and DALY rates in men aged ≥ 60 years increased with age, peaking at 92 years old, and then decreased further with increases in age ( 16 , 17 ). The MM prevalence and incidence rates also showed an increasing trend with time. Over time, the MM DALY rate showed an overall upward trend, with a slight decrease from 2004 to 2009 ( 18 ). Before 1902, the MM prevalence, incidence, and DALY rates decreased with increases in the birth cohort, demonstrating an upward trend thereafter. After 1923, the DALY rate generally showed a downward trend, likely due to medical advancements (Fig. 7 ). Discussion The MM prevalence and incidence rates have been established to increase globally with the ageing of the population. Furthermore, MM, a malignant plasma cell disease, is mostly prevalent in middle-aged and elderly populations, and enhanced osteoclast activity and suppressed osteoblast function have been established as the primary pathological mechanisms of Multiple Myeloma Bone Disease (MMBD). It is also noteworthy that advanced age is an important risk factor for MM, with elderly men living in high-income countries having the highest prevalence of the disease. Notably, MM imposes a huge burden on patients’ physical and mental health. Specifically, ≥ 30% and ≥ 60% of MM patients reported severe impacts of the disease on their work/life and psychological profile, respectively. Furthermore, ⁓50% of patients reported that current MM treatments do not meet their needs regarding overall outcomes and survival benefits; hence, there are presently high expectations among MM patients for more effective novel treatments. Over the past decades, the incidence of MM has shown an upward trend, with developed regions exhibiting a more significant increase. This phenomenon could be attributed to population growth and ageing, improved diagnostics, and increased GDP/capita. Additionally, over the past 32 years, there has been a global increase in diagnosis rates owing to the efforts of healthcare professionals and advances in detection and diagnostic techniques. It is also noteworthy that there has been regional variability in diagnostic capabilities and rates due to the differences in levels level of economic development and medical care standards. Herein, SDI variations correlated with MM prevalence, morbidity, mortality, and DALY rates. Countries with low socio-economic development, especially those in sub-Saharan Africa, demonstrated very limited access to effective treatment. There were also differences in the primary treatment options, with Autologous Stem Cell Transplantation (ASCT) being the main intervention in the United States and Europe. Additionally, among the examined countries, China had the highest MM prevalence, incidence, and DALY rates, a phenomenon attributable to its huge population base, rapid economic development, medical care advances, and improvements in people's living standards and health concerns. The United States also had relatively high MM prevalence, incidence, and DALY rates, potentially due to its significant ageing population ( 19 , 20 ). Survival outcomes also varied among MM patients, with an Overall Survival (OS) of > 10 years in patients suitable for transplantation and a lower median survival of ⁓5 years in older patients. These differences could be attributed to variations in the levels of diagnosis and treatment, environmental norms, and metabolic disease prevalence rates across different regions. With advances in therapeutic approaches, the OS and prognosis of MM patients are likely to improve quite significantly compared to past situations, although the ideal treatment goal of eradication remains elusive and patients are still at a huge risk of recurrence of the primary disease over time ( 21 ). Improvements are also likely to be complicated by the fact that the etiology of MM encompasses various factors, including genetic predisposition, ionizing radiation exposure, infections, exposure to harmful chemicals, prolonged and repeated inflammatory stimuli, and the presence or absence of previous autoimmune-related disorders ( 22 ). Although MM is still considered a single disease, it is a malignant tumour encompassing cells from several cytogenetically distinct plasma cell clones ( 23 , 24 ). Moreover, almost all MM patients eventually relapse. Consequently, tailored interventions may be required for MM patients. For instance, standard- and high-risk MM patients may require lenalidomide and bortezomib + lenalidomide maintenance therapies, respectively ( 25 , 26 ). Furthermore, in treating a recurrent disease, triple-treatment regimens may be administered, with the regimen choice varying across patients. Some of the options include Chimeric Antigen Receptor T (CAR-T) Cell Immunotherapy and bispecific antibodies ( 27 , 28 ). Nonetheless, these treatment regimens may yield minimal benefits in elderly MM patients, especially those aged ≥ 60 years, probably due to poor tolerability, adverse chemotherapy effects, a highly malignant myeloma cell biology, and unavailability of hematopoietic stem cells for transplantation. Due to the stress of potential relapse, MM patients may further experience multiple challenges regarding their physical and mental well-being and QoL, despite the available therapies. These insights highlight the need for more attention and research into novel strategies, ultimately improving the treatment and QoL of MM patients. Limitations Despite its valuable insights, this study had several limitations. First, the estimates presented in this paper are not comprehensive, potentially due to lower care standards in some countries and potential risks of misdiagnosis and underdiagnosis in underdeveloped countries, leading to an underestimation of the disease burden. Second, GBD-derived data relies heavily on modelling algorithms as the database’s collaborators utilize various statistical modelling methods, especially in some countries with limited raw data. Third, the MM burden is a complex concept as the definition of disability weights remains significantly one-sided and the "measurability" of disability remains complex. Therefore, attention should be paid to the lagging nature of GBD data and more practical real-world research should be conducted to validate the results and for more accurate and comprehensive assessments. Conclusions There has been a significant increase in the MM burden among men aged ≥ 60 years, necessitating increased healthcare investments. Owing to therapeutic advancements, MM in men aged ≥ 60 years is presently being treated with high-dose chemotherapy or autologous hematopoietic stem cell transplantation. Although these interventions could somewhat prolong patient survival, some of them have been associated with a poor prognosis and increased risk of death, depending on the physical conditions of the elderly patients. Therefore, the therapeutic efficacy of these interventions should be maximized in healthier elderly patients. On the other hand, attempts should be made to reduce their toxicity in general and frail patients and lower the risk of discontinuing the drugs mid-treatment, thus prolonging the patients' survival as much as possible and improving their QoL. Moreover, updating the global data on the MM burden in men aged ≥ 60 years is imperative to keep policymakers appraised of the latest developments, thus aiding in developing more efficient prevention and control strategies. Declarations Acknowledgements Not applicable. Authors' contributions SH searched and summarized the research. LYX was responsible for the selection of literature. FLJ, JYN, ZGD, RQ, LXT, and ZYC were responsible for drafting the manuscript. SZX put forward the concepts of the study. All the authors revised the manuscript. All the authors approved the final manuscript. Funding Funding was provided by the National Natural Science Foundation of China (No. 82104618); Shi Zhexin Tianjin Famous Traditional Chinese Medicine Inheritance Studio (tjmzy2406). Availability of data and materials Not applicable. Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare that they have no conflicts of interest. Author details The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Centre for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China Generative AI and AI-assisted technologies were NOT used in the preparation of this work. References Teixeira MX, Reis AMM, Drummond PLM et al (2024) Incidence and reasons for discontinuation of first-line therapy in patients with multiple myeloma: results from a historical cohort, Brazil 2009–2020. Ann Hematol. 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Supplementary Files Tables.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 01 May, 2026 Reviews received at journal 18 Mar, 2026 Reviewers agreed at journal 12 Mar, 2026 Reviewers invited by journal 12 Mar, 2026 Editor assigned by journal 02 Jan, 2026 Submission checks completed at journal 02 Jan, 2026 First submitted to journal 26 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8453482","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":605629267,"identity":"28f2fbcd-24b3-424b-a248-707862ac0c9a","order_by":0,"name":"Hui Sun","email":"","orcid":"","institution":"The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, National Medical Center, National Clinical Research Centre for Chinese Medicine Acupuncture and 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Shi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzUlEQVRIiWNgGAWjYDACCQY2BgYDGx7G9sbGhx+I11KRJsfcc7jZWIJ4LWcOGbPPSG8T4CFGh/zs9mePedsOJPbOfNgG1G8np9tAQIvBnQPphjPb7iTOnJ3Y9qCAIdnY7AAhLRIJxyQ+tj1L3Dg7sd1AguFA4jZCWuRnJLZJJLYdTtx/82CbBA8xWhhuJLNJfDhz2JhxBiORWgxupLFJzgAGMmNPIjCQDYjwi/yM9GfSPOCoPP7w4YcKOzmCWtAtJU35KBgFo2AUjAIcAABSh0alD0bzYwAAAABJRU5ErkJggg==","orcid":"","institution":"The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, National Medical Center, National Clinical Research Centre for Chinese Medicine Acupuncture and Moxibustion","correspondingAuthor":true,"prefix":"","firstName":"Zhexin","middleName":"","lastName":"Shi","suffix":""}],"badges":[],"createdAt":"2025-12-26 08:23:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8453482/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8453482/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104872591,"identity":"abcec250-8a62-40fe-bbeb-4f51aafce04e","added_by":"auto","created_at":"2026-03-18 08:22:32","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":85964,"visible":true,"origin":"","legend":"\u003cp\u003eTrend of MM burden in men ≥ 60 years in global and 5 SDI regions.\u003cstrong\u003e A \u003c/strong\u003eThe prevalence trend from 1990 to 2021. \u003cstrong\u003eB\u003c/strong\u003e The trend of prevalence rates from 1990 to 2021.\u003cstrong\u003e C\u003c/strong\u003e The DALYs trend from 1990 to 2021.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8453482/v1/33b57d88548f0e4f335654f4.jpg"},{"id":104872594,"identity":"1115b11a-eb75-49e9-8444-1b1598829afb","added_by":"auto","created_at":"2026-03-18 08:22:32","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":102026,"visible":true,"origin":"","legend":"\u003cp\u003eThe EAPC of MM burden in men ≥ 60 years in 5 SDI and 21 regions.\u003cstrong\u003e A \u003c/strong\u003eThe EAPC of prevalence rates from 1990 to 2021.\u003cstrong\u003e B \u003c/strong\u003eThe EAPC of incidence rates from 1990 to 2021.\u003cstrong\u003e C \u003c/strong\u003eThe EAPC of DALY rates from 1990 to 2021.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8453482/v1/8e9b388c99dc6b9f12d3180c.jpg"},{"id":104872596,"identity":"b7344d33-d543-491a-b9e8-03e60b4febf5","added_by":"auto","created_at":"2026-03-18 08:22:33","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":162100,"visible":true,"origin":"","legend":"\u003cp\u003eThe EAPC of MM burden in men ≥ 60 years globally.\u003cstrong\u003e A \u003c/strong\u003eThe EAPC of \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eprevalence rates in 204 countries from 1990 to 2021. \u003cstrong\u003eB \u003c/strong\u003eThe EAPC of\u003cstrong\u003e \u003c/strong\u003eincidence rates in 204 countries from 1990 to 2021.\u003cstrong\u003e C \u003c/strong\u003eThe EAPC of DALY rates in 204 countries from 1990 to 2021.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8453482/v1/c96141127188a7be93658dd3.jpg"},{"id":104872597,"identity":"c378008f-5909-40fe-afc7-4a1aa2beea22","added_by":"auto","created_at":"2026-03-18 08:22:33","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":245643,"visible":true,"origin":"","legend":"\u003cp\u003eThe Age patterns of MM burden in men ≥ 60 years in different regions in 2021. \u003cstrong\u003eA \u003c/strong\u003eThe Age patterns of prevalence rates.\u003cstrong\u003e B \u003c/strong\u003eThe Age patterns of incidence rates.\u003cstrong\u003e C \u003c/strong\u003eThe Age patterns of DALY rates.\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8453482/v1/a4bcd397b5efee72dd9a1236.jpg"},{"id":105033848,"identity":"633b43f1-90c8-48a1-84d9-8d8f2e44f5d4","added_by":"auto","created_at":"2026-03-20 07:21:56","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":129909,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e The associations between the SDI and prevalence rates per 100,000 population of MM in men ≥ 60 years across 21 GBD regions. \u003cstrong\u003eB\u003c/strong\u003e The associations between the SDI and incidence rates per 100,000 population of MM in men ≥ 60 years across 21 GBD regions. \u003cstrong\u003eC\u003c/strong\u003e The associations between the SDI and DALY rates per 100,000 population of MM in men ≥ 60 years across 21 GBD regions.\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8453482/v1/93a8d30906b05c290b29060f.jpg"},{"id":104872593,"identity":"95a413cb-1b38-4795-96fd-cb15d9427ffa","added_by":"auto","created_at":"2026-03-18 08:22:32","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":125150,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA \u003c/strong\u003eAAPC analysis of the MM prevalence rate. \u003cstrong\u003eB \u003c/strong\u003eAAPC analysis of the MM incidence rate. \u003cstrong\u003eC \u003c/strong\u003eAAPC analysis of the MM DALY rate.\u003c/p\u003e","description":"","filename":"6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8453482/v1/652fb59e0c7fb06a9f7c01af.jpg"},{"id":104872598,"identity":"9234bb11-2880-4784-94ee-3d6bc0b3e95b","added_by":"auto","created_at":"2026-03-18 08:22:33","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":129629,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e APC of prevalence rates.\u003cstrong\u003e B\u003c/strong\u003e APC model of incidence rates.\u003cstrong\u003e C\u003c/strong\u003e APC model of DALY rates.\u003c/p\u003e","description":"","filename":"7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8453482/v1/ba22083d6b82a285bd820ce7.jpg"},{"id":106993817,"identity":"83a666d0-b78f-4d0e-9d48-aac035c5c209","added_by":"auto","created_at":"2026-04-15 14:57:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1610285,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8453482/v1/4af85cc2-48fb-4b05-b0ce-45d24439f468.pdf"},{"id":104872592,"identity":"79268bf7-63a8-40a2-b267-10c574e1ee21","added_by":"auto","created_at":"2026-03-18 08:22:32","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":148986,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-8453482/v1/509b74115177e0b2e0f1393b.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Global, Regional, and National Burdens and Trends of Multiple Myeloma in Men Aged 60 Years and Older: An Analysis using the Global Burden of Disease Database (1990-2021)","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMultiple Myeloma (MM), a hematological tumour characterized by malignant clonal plasma cell proliferation in the bone marrow, remains incurable and is presently the second most prevalent among hematological tumours (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Significant progress has recently been realized in MM treatment, with combination chemotherapy interventions increasingly being employed to clinically prolong MM patients\u0026rsquo; survival and improve their Quality of Life (QoL) (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Nonetheless, most MM patients still end up with disease recurrence, a phenomenon partly attributable to the fact that MM is a heterogeneous plasma cell malignant disease. This heterogeneity could be attributed to the different biological characteristics of the patients and is mainly reflected in clinical features and patient survival outcomes (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eNotably, MM-related morbidity and mortality rates have been established to be particularly higher among men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years, with both Age-Standardized Incidence Rate (ASIR) and Age-Standardized Mortality Rate (ASMR) increasing with age. Furthermore, there is a 1.5- to 2-fold gender-specific difference in ASIR and ASMR, with the rates consistently higher in men than in women. Therefore, this study aimed to examine the MM burden in men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData sources\u003c/h2\u003e \u003cp\u003eHerein, global health data (from 1990 to 2021) of male MM patients aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years was retrieved from the Global Burden of Disease (GBD) database, including global, regional, and national incidence rates and counts, mortality rates and counts, and Disability-Adjusted Life Year (DALY) rates and counts. The above data were integrated using the Bayesian meta-regression tool DisMod-MR2.1, yielding internally consistent morbidity and mortality rates with 95% Uncertainty Intervals (95% UIs)) (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Notably, as a measure of disease burden, DALYs comprise two components: Years of Life Lost (YLLs) and Years of Life Lived with Disability (YLDS) (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). In this study, elderly MM patients aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years were categorized into eight age groups: 60\u0026ndash;64, 65\u0026ndash;69, 70\u0026ndash;74, 75\u0026ndash;79, 80\u0026ndash;84, 85\u0026ndash;89,90\u0026ndash;94, and \u0026ge;\u0026thinsp;95 years. Furthermore, based on the Socio-Demographic Index (SDI), 204 countries and territories were identified and divided into five categories, ranging from low to high SDI (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). For a comprehensive analysis, the global map was further divided into 21 regions based on geographic locations.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStatistical methods\u003c/h3\u003e\n\u003cp\u003eLinear regression could be useful in estimating trends across various indicators over time in public health and epidemiological studies. However, the actual time series data may be more complex. Therefore, in this study, we determined the Estimated Annual Percentage Change (EAPC) values and their corresponding 95% UIs using linear regression (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Notably, the EAPC values could depict trends in MM prevalence, incidence, and DALY rates (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Herein, both the EAPC value and the lower bound of the 95% Confidence Interval (CI) being \u0026gt;\u0026thinsp;0 indicated an upward trend in the disease rates among the elderly population. Conversely, both the EAPC value and upper boundary of the 95% CI being \u0026lt;\u0026thinsp;0 indicated a decreasing trend in the disease rates. The SDI, a composite index often used to assess the level of socio-economic development in a country, was also used in this study as a measure. We determined the correlation coefficients between SDI and both EAPC and the incidence rates, with higher correlation coefficients indicating a closer relationship. Statistical analyses were performed using R software, with multiple R packages used for data processing and visualization. The global burden of MM patients in men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years was depicted using a world map, showing the burden of the disease in 204 countries and 21 regions. Results or differences with p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant. Average annual percentage change (AAPC) model was conducted a further assessment. The age-period-cohort (APC) model was used to further examine the effects of age, period, and birth cohort on changes in MM prevalence, incidence, and DALY rates over the past 30 years (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eGlobal level\u003c/h2\u003e \u003cp\u003eGlobally, the prevalence, incidence, and DALYs of MM in men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years have all increased significantly. Specifically, from 1990 to 2021, the MM prevalence, incidence, and DALY cases increased from 41,667 to 159,923, 21,071 to 64,181, and 379,760 to 980993, respectively. Furthermore, from 1990 to 2021, the MM incidence, prevalence, and DALY rates in males aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years all increased, with EAPC values of 0.72% (95% CI: 0.63 to 0.82), 1.70% (95% CI: 1.50 to 1.90), and 0.22% (95% CI: 0.14 to 0.29), respectively. These findings suggest a general upward trend in the MM burden in men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years(Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSDI regional level\u003c/h3\u003e\n\u003cp\u003eIn 2021, men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years had the highest MM prevalence, incidence, and DALY cases. Furthermore, the high SDI region exhibited the highest MM prevalence, incidence, and DALY rates in 2021, accounting for ⁓50% of total global cases. Additionally, from 1990 to 2021, the MM prevalence, incidence, and DALY rates in the Middle SDI region showed a rapid upward trend, with EAPC values of 3.49 (95% CI: 3.35 to 3.62), 2.46 (95% CI:2.31 to 2.62), and 2.03 (95% CI:1.85 to 2.21), respectively(Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eGBD regional level\u003c/h2\u003e \u003cp\u003eOver time, men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years demonstrated increases in the MM prevalence, incidence, and DALY rates across all regions. Furthermore, over the past 32 years, increases in the MM prevalence and DALY rates have been observed in most regions, with East Asia and Eastern Europe demonstrating the largest increases, showing EAPC values of 6.14 (95% CI: 5.58 to 6.71) and 2.97 (95% CI: 2.48 to 3.47) for prevalence and 3.47 (95% CI: 2.78 to 4.16) and 1.49 (95% CI: 1.18 to 1.80) for DALY, respectively. Conversely, Oceania showed a decline in both the MM prevalence and DALY rates, with EAPC values of -0.25 (95% CI: -0.34 to -0.16) and \u0026minus;\u0026thinsp;0.33 (95% CI: -0.41 to -0.25), respectively. Moreover, the MM prevalence and DALY rates among men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years from high-income Asia-Pacific and North American regions showed opposite trends, with EAPC values of 0.94 (95% CI: 0.77 to 1.12) and 0.77 (95% CI: 0.52 to 1.03) for prevalence and \u0026minus;\u0026thinsp;0.83 (95% CI: -0.96 to -0.69) and \u0026minus;\u0026thinsp;0.71 (95% CI:-0.82 to -0.60) for DALY, respectively. This trend could be attributed to local healthcare standards and economic conditions(Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eCountry level\u003c/h2\u003e \u003cp\u003eThe MM incidence, prevalence, and DALY rates in men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years also varied significantly across the globe by country. For MM incidence, prevalence, and DALY rates, China and the United States had the highest and lowest EAPC values, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eAge patterns\u003c/h2\u003e \u003cp\u003eIn 2021, 21 regions recorded the lowest MM prevalence rate among men aged\u0026thinsp;\u0026ge;\u0026thinsp;95 years, as well as the lowest MM incidence rate among men aged 60\u0026ndash;64 years. Oceania had the lowest DALY rate among men aged\u0026thinsp;\u0026ge;\u0026thinsp;95 years. The MM prevalence, incidence, and death rates among men aged 60\u0026ndash;74 years correlated positively with age, but decreased with further increases in age. Similarly, the MM DALY rate in men aged 60\u0026ndash;69 years correlated positively with age but decreased with further increases in age (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec23\" class=\"Section3\"\u003e \u003ch2\u003eAssociation between MM burden and SDI\u003c/h2\u003e \u003cp\u003eIn 2021, the MM prevalence, incidence, and DALY rates in men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years correlated positively with SDI. With advancements in the global economy, the overall burden of the disease has risen, and the global burden of MM in men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years has reached unexpectedly high levels. Across the 21 regions, the burden of MM in men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years was relatively stable when SDI values remained between 0.3 and 0.5. However, it peaked when the SDI value reached 0.9, especially among male MM patients aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years. Regionally, the MM burden was unexpectedly higher in Western Europe and unexpectedly lower in Eastern Europe, Central Asia, and Southeast Asia. Nationally, New Zealand, Canada, and Australia demonstrated higher-than-expected MM burdens in men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years, while Yemen, the Gambia, and the United States had lower-than-expected MM burdens (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec27\" class=\"Section3\"\u003e \u003ch2\u003eAAPC analysis of the MM prevalence, incidence, and DALY rates\u003c/h2\u003e \u003cp\u003eThe global prevalence rate and incidence rate of AAPC showed an upward trend from 1990 to 2017, and a downward trend after 2017. The AAPC of DALY rate showed an upward trend from 1990 to 2002, a downward trend from 2002 to 2006, and a straight upward trend after 2006 (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e\u003cdiv id=\"Sec31\" class=\"Section2\"\u003e \u003ch2\u003eAge-period-cohort analysis of the MM prevalence, incidence, and DALY rates\u003c/h2\u003e \u003cp\u003eThe MM prevalence, incidence, and DALY rates in men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years increased with age, peaking at 92 years old, and then decreased further with increases in age (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The MM prevalence and incidence rates also showed an increasing trend with time. Over time, the MM DALY rate showed an overall upward trend, with a slight decrease from 2004 to 2009 (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Before 1902, the MM prevalence, incidence, and DALY rates decreased with increases in the birth cohort, demonstrating an upward trend thereafter. After 1923, the DALY rate generally showed a downward trend, likely due to medical advancements (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe MM prevalence and incidence rates have been established to increase globally with the ageing of the population. Furthermore, MM, a malignant plasma cell disease, is mostly prevalent in middle-aged and elderly populations, and enhanced osteoclast activity and suppressed osteoblast function have been established as the primary pathological mechanisms of Multiple Myeloma Bone Disease (MMBD). It is also noteworthy that advanced age is an important risk factor for MM, with elderly men living in high-income countries having the highest prevalence of the disease. Notably, MM imposes a huge burden on patients\u0026rsquo; physical and mental health. Specifically, \u0026ge; 30% and \u0026ge;\u0026thinsp;60% of MM patients reported severe impacts of the disease on their work/life and psychological profile, respectively. Furthermore, ⁓50% of patients reported that current MM treatments do not meet their needs regarding overall outcomes and survival benefits; hence, there are presently high expectations among MM patients for more effective novel treatments.\u003c/p\u003e \u003cp\u003eOver the past decades, the incidence of MM has shown an upward trend, with developed regions exhibiting a more significant increase. This phenomenon could be attributed to population growth and ageing, improved diagnostics, and increased GDP/capita. Additionally, over the past 32 years, there has been a global increase in diagnosis rates owing to the efforts of healthcare professionals and advances in detection and diagnostic techniques. It is also noteworthy that there has been regional variability in diagnostic capabilities and rates due to the differences in levels level of economic development and medical care standards. Herein, SDI variations correlated with MM prevalence, morbidity, mortality, and DALY rates. Countries with low socio-economic development, especially those in sub-Saharan Africa, demonstrated very limited access to effective treatment. There were also differences in the primary treatment options, with Autologous Stem Cell Transplantation (ASCT) being the main intervention in the United States and Europe.\u003c/p\u003e \u003cp\u003eAdditionally, among the examined countries, China had the highest MM prevalence, incidence, and DALY rates, a phenomenon attributable to its huge population base, rapid economic development, medical care advances, and improvements in people's living standards and health concerns. The United States also had relatively high MM prevalence, incidence, and DALY rates, potentially due to its significant ageing population (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSurvival outcomes also varied among MM patients, with an Overall Survival (OS) of \u0026gt;\u0026thinsp;10 years in patients suitable for transplantation and a lower median survival of ⁓5 years in older patients. These differences could be attributed to variations in the levels of diagnosis and treatment, environmental norms, and metabolic disease prevalence rates across different regions. With advances in therapeutic approaches, the OS and prognosis of MM patients are likely to improve quite significantly compared to past situations, although the ideal treatment goal of eradication remains elusive and patients are still at a huge risk of recurrence of the primary disease over time (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Improvements are also likely to be complicated by the fact that the etiology of MM encompasses various factors, including genetic predisposition, ionizing radiation exposure, infections, exposure to harmful chemicals, prolonged and repeated inflammatory stimuli, and the presence or absence of previous autoimmune-related disorders (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough MM is still considered a single disease, it is a malignant tumour encompassing cells from several cytogenetically distinct plasma cell clones (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Moreover, almost all MM patients eventually relapse. Consequently, tailored interventions may be required for MM patients. For instance, standard- and high-risk MM patients may require lenalidomide and bortezomib\u0026thinsp;+\u0026thinsp;lenalidomide maintenance therapies, respectively (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Furthermore, in treating a recurrent disease, triple-treatment regimens may be administered, with the regimen choice varying across patients. Some of the options include Chimeric Antigen Receptor T (CAR-T) Cell Immunotherapy and bispecific antibodies (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Nonetheless, these treatment regimens may yield minimal benefits in elderly MM patients, especially those aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years, probably due to poor tolerability, adverse chemotherapy effects, a highly malignant myeloma cell biology, and unavailability of hematopoietic stem cells for transplantation. Due to the stress of potential relapse, MM patients may further experience multiple challenges regarding their physical and mental well-being and QoL, despite the available therapies. These insights highlight the need for more attention and research into novel strategies, ultimately improving the treatment and QoL of MM patients.\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eDespite its valuable insights, this study had several limitations. First, the estimates presented in this paper are not comprehensive, potentially due to lower care standards in some countries and potential risks of misdiagnosis and underdiagnosis in underdeveloped countries, leading to an underestimation of the disease burden. Second, GBD-derived data relies heavily on modelling algorithms as the database\u0026rsquo;s collaborators utilize various statistical modelling methods, especially in some countries with limited raw data. Third, the MM burden is a complex concept as the definition of disability weights remains significantly one-sided and the \"measurability\" of disability remains complex. Therefore, attention should be paid to the lagging nature of GBD data and more practical real-world research should be conducted to validate the results and for more accurate and comprehensive assessments.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThere has been a significant increase in the MM burden among men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years, necessitating increased healthcare investments. Owing to therapeutic advancements, MM in men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years is presently being treated with high-dose chemotherapy or autologous hematopoietic stem cell transplantation. Although these interventions could somewhat prolong patient survival, some of them have been associated with a poor prognosis and increased risk of death, depending on the physical conditions of the elderly patients. Therefore, the therapeutic efficacy of these interventions should be maximized in healthier elderly patients. On the other hand, attempts should be made to reduce their toxicity in general and frail patients and lower the risk of discontinuing the drugs mid-treatment, thus prolonging the patients' survival as much as possible and improving their QoL. Moreover, updating the global data on the MM burden in men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years is imperative to keep policymakers appraised of the latest developments, thus aiding in developing more efficient prevention and control strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSH searched and summarized the research. LYX was responsible for the selection of literature. FLJ, JYN, ZGD, RQ, LXT, and ZYC were responsible for drafting the manuscript. SZX put forward the concepts of the study. All the authors revised the manuscript. All the authors approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFunding was provided by the National Natural Science Foundation of China (No. 82104618); Shi Zhexin Tianjin Famous Traditional Chinese Medicine Inheritance Studio (tjmzy2406).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Centre for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China\u003c/p\u003e\n\u003cp\u003eGenerative AI and AI-assisted technologies were NOT used in the preparation of this work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTeixeira MX, Reis AMM, Drummond PLM et al (2024) Incidence and reasons for discontinuation of first-line therapy in patients with multiple myeloma: results from a historical cohort, Brazil 2009\u0026ndash;2020. Ann Hematol. Mar 9\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLim U, Freedman DM, Hollis BW et al (2009) A prospective investigation of serum 25-hydroxyvitamin D and risk of lymphoid cancers. Int J Cancer 124(4):979\u0026ndash;986\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDiaz-delCastillo M, Chantry AD, Lawson MA et al (2021) Multiple myeloma-A painful disease of the bone marrow. Semin Cell Dev Biol 112:49\u0026ndash;58\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDou X, Duan G, Zhong Y, Liu Y, Peng N, Wen L, Qi J, Zhou M, Zhang X, Lu J (2025) The burden of multiple myeloma in China: Trends from 1990 to 2021 and forecasts for 2050. Cancer Lett 611:217440\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCowan AJ, Green DJ, Kwok M et al (2022) Diagnosis and Management of Multiple Myeloma: A Review. JAMA 327(5):464\u0026ndash;477\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu J, Liu W, Mi L et al (2019) Incidence and mortality of multiple myeloma in China, 2006\u0026ndash;2016: an analysis of the Global Burden of Disease Study 2016. j Hematol Oncol 12(1):136\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu Z, Xia F, Lin R (2024) Global burden of cancer and associated risk factors in 204 countries and territories, 1980\u0026ndash;2021: a systematic analysis for the GBD 2021. J Hematol Oncol 17(1):119\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGBD 2021 Diseases and Injuries Collaborators (2024) Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990\u0026ndash;2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet 403(10440):2133\u0026ndash;2161\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao S, Wang H, Chen H et al (2022) Global magnitude and long-term trend of ischemic heart disease burden attributed to household air pollution from solid fuels in 204 countries and territories, 1990\u0026ndash;2019. Indoor Air 32(2):e12981\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang H, Zhao S, Wang S et al (2022) Global magnitude of encephalitis burden and its evolving pattern over the past 30 years. J Infect 84(6):777\u0026ndash;787\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang K, Kan C, Han F et al (2023) Global, Regional, and National Epidemiology of Diabetes in Children From 1990 to 2019. JAMA Pediatr 177(8):837\u0026ndash;846\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCen J, Wang Q, Cheng L, Gao Q, Wang H, Sun F (2024) Global, regional, and national burden and trends of migraine among women of childbearing age from 1990 to 2021. Insights from the Global Burden of Disease Study 2021. J Headache Pain 25(1):96\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang X, Chen H, Zhang T et al (2021) Global, regional, and national burden of blindness and vision loss due to common eye diseases along with its attributable risk factors from 1990 to 2019: a systematic analysis from the global burden of disease study 2019. Aging 13(15):19614\u0026ndash;19642\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang L, Tong Z, Han R et al (2023) Spatiotemporal trends in global burden of rheumatic heart disease and associated risk factors from 1990 to 2019. Int J Cardiol 384:100\u0026ndash;106\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeng Q, Jiang D (2023) Global trends of interstitial lung diseases from 1990 to 2019: an age-period-cohort study based on the Global Burden of Disease study 2019, and projections until 2030. Front Med (Lausanne) 10:1141372\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFan L, Wu Y, Wei J et al (2023) Global, regional, and national time trends in incidence for migraine, from 1990 to 2019: an age-period-cohort analysis for the GBD 2019. J Headache Pain 24(1):79\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang D, Lai H, Shi X et al (2024) Global temporal trends and projections of acute hepatitis E incidence among women of childbearing age: Age-period-cohort analysis 2021. J Infect 89(4):106250\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang F, Cui Y, Gao X (2023) Time trends in the burden of autoimmune diseases across the BRICS: an age-period-cohort analysis for the GBD 2019. RMD Open 9(4):e003650\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFaul JD, Kim JK, Levine ME et al (2023) Epigenetic-based age acceleration in a representative sample of older Americans. Associations with aging-related morbidity and mortality. Proc Natl Acad Sci U S A 120(9):e2215840120\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarcia Morales EE, Reed NS, Zhou Y et al (2024) Population prevalence of dual sensory loss in community-dwelling US adults 71 years and older: Evidence from the National Health and Aging Trends Study. J Am Geriatr Soc 72(2):536\u0026ndash;543\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRajkumar SV (2024) Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management. Am J Hematol 99(9):1802\u0026ndash;1824\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhu K, Li Y, Deng C et al (2020) Significant association of PKM2 and NQO1 proteins with poor prognosis in breast cancer. Pathol Res Pract 216(11):153173\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKumar SK, Rajkumar SV (2018) The multiple myelomas - current concepts in cytogenetic classification and therapy. Nat Rev Clin Oncol 15(7):409\u0026ndash;421\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoreau P, Rajkumar SV (2016) Multiple myeloma-translation of trial results into reality. Lancet 388(10040):111\u0026ndash;113\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRajkumar SV, Hayman SR, Lacy MQ et al (2005) Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 106(13):4050\u0026ndash;4053\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRichardson PG, Blood E, Mitsiades CS et al (2006) A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood 108(10):3458\u0026ndash;3464\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCohen AD, Garfall AL, Stadtmauer EA et al (2019) B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma. j Clin Invest 129(6):2210\u0026ndash;2221\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRajkumar SV (2024) Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management. Am J Hematol 99(9):1802\u0026ndash;1824\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 3 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"MM, Burden of Disease, men aged ≥ 60 years, DALYs, Age-period-cohort analysis, GBD 2021","lastPublishedDoi":"10.21203/rs.3.rs-8453482/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8453482/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eMultiple Myeloma (MM) is the second most prevalent hematological disease worldwide. In light of rapid advances in medical technologies and complex socioeconomic circumstances, a report detailing the latest epidemiological patterns of MM in men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years would be vital for policymakers to ensure judicious healthcare resource use and allocation, forming the basis of this study. Herein, we analyzed data from the Global Burden of Disease (GBD) database (from 1990 to 2021). We specifically focused on four key MM-related indicators, including prevalence, incidence, Disability-Adjusted Life-Years (DALYs), and Estimated Annual Percentage Change (EAPC). The data were largely presented as estimated 95% Uncertainty Intervals (UI). The age-period-cohort (APC) and Average annual percentage change (AAPC) model was used for further analysis. In 2021, the global MM prevalence, incidence, and DALYs in men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years were approximately 159,923, 64,181, and 980,993, respectively. Furthermore, over the past 32 years, the global MM prevalence, incidence, and DALY rates have increased, with EAPC values of 1.70 (95% UI: 1.50\u0026thinsp;~\u0026thinsp;1.90), 0.72 (95% UI: 0.63\u0026thinsp;~\u0026thinsp;0.82), and 0.22 (95% UI: 0.14\u0026thinsp;~\u0026thinsp;0.29), respectively. It is also noteworthy that in 2021, among the five Socio-Demographic Index (SDI) regions, the MM prevalence (91,233), incidence (33,288), and DALYs (44,767,678) in men aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years were the largest number in the high SDI regions, accounting for ⁓50% of the global total. This phenomenon highlights the significance of tailored interventions for MM patients, aligning with several World Health Organization\u0026rsquo;s (WHO) sustainable development goals.\u003c/p\u003e","manuscriptTitle":"Global, Regional, and National Burdens and Trends of Multiple Myeloma in Men Aged 60 Years and Older: An Analysis using the Global Burden of Disease Database (1990-2021)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-18 08:22:21","doi":"10.21203/rs.3.rs-8453482/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-01T07:55:37+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-18T05:22:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"75658819314231596014154380280855809124","date":"2026-03-12T13:28:08+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-12T09:50:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-02T08:58:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-02T08:56:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"Annals of Hematology","date":"2025-12-26T08:15:13+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"40c847ad-cdf3-425b-8221-3dd09acffd24","owner":[],"postedDate":"March 18th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-01T07:55:37+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-14T05:38:14+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-18 08:22:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8453482","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8453482","identity":"rs-8453482","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}