1. Global Epidemiologic Burden and Distribution
Multiple myeloma (MM) is a clonal plasma cell malignancy accounting for approximately 1–2% of all cancers and 10–15% of all hematological malignancies worldwide 24. It ranks as the second most common hematologic cancer in several regions, including Europe 25. Over the past three decades, the global burden has expanded dramatically: in 2021, approximately 148,755 new MM cases were recorded globally (95% uncertainty interval [UI]: 131,780–162,049), with 116,360 deaths (95% UI: 103,079–128,471) and 2,595,595 disability-adjusted life-years (DALYs) 257. The global age-standardized incidence rate (ASIR) reached 1.74 per 100,000 (95% UI: 1.54–1.89) in 2021 228, while the age-standardized prevalence rate (ASPR) was 4.55 per 100,000, reflecting a 218% increase since 1990 28.
Marked geographic disparities characterize MM epidemiology. High-SDI (sociodemographic index) regions—primarily North America, Europe, and Australasia—bear the greatest absolute and age-standardized burden, whereas low-SDI regions report substantially lower rates but exhibit accelerating trends consistent with epidemiologic transition 27. The following table summarizes regional age-standardized rates:
| Region | ASIR (per 100,000) | ASMR (per 100,000) | Reference Year |
|---|---|---|---|
| Global | 1.74 | 1.37 | 2021 |
| Australasia | 5.8 | ~1.8 | 2016 |
| High-income North America | ~5.2–7.4 | 2.8 | 2016–2023 |
| Western Europe | 4.6 | Variable | 2016 |
| Germany | 3.7 (F), 5.5 (M) | 1.8 (F), 2.9 (M) | 2020 |
| Italy | ~4.0 | 2.47 | 2023 |
| Switzerland | 4.7–5.0 | Stable | 2009–2013 |
| Russia | 1.81 | ~1.2 | 2021 |
| China | 0.81–1.03 | 0.6–0.67 | 2016–2021 |
The United States reported an age-adjusted incidence rate of 7.4 per 100,000 per year (2019–2023 data), with approximately 36,000 new cases and 10,850 deaths projected for 2026 24. As of 2023, an estimated 202,793 people were living with MM in the United States, underscoring the chronic and survivable nature of modern MM 24. China, by contrast, recorded approximately 17,250 new cases and 12,984 deaths in 2021, with an ASIR of 0.81 per 100,000—among the lowest of the major economies studied—reflecting a combination of true lower baseline risk and historical underdiagnosis in less-developed provinces 14.
2. Temporal Trends Over the Past Decade
Global MM incidence, prevalence, mortality, and DALYs have risen consistently since 1990, driven by population aging and growth. From 1990 to 2021, ASIR increased from 1.47 to 1.74 per 100,000 (average annual percentage change [AAPC]: +0.55%), while age-standardized mortality rate (ASMR) rose from 1.29 to 1.37 per 100,000 (AAPC: +0.20%) 2. In adults aged 40 and older, temporal trends from 1990 to 2021 showed AAPCs of +0.53% for incidence, +1.2% for prevalence, +0.19% for mortality, and +0.15% for DALYs 22.
Critically, mortality trends diverge sharply by development level. High-SDI countries have achieved declining ASMR (AAPC: −0.51%), whereas middle-SDI countries demonstrate the steepest mortality increases (AAPC: +1.91%) 2. In the United States specifically, mortality has declined at an average annual rate of 3.0% over 2015–2024, with the 5-year relative survival rising from approximately 26% in 1975 to 63.7% in 2016–2022 24. This improvement reflects the sequential introduction of immunomodulatory drugs (thalidomide, lenalidomide, pomalidomide), proteasome inhibitors (bortezomib, carfilzomib), and anti-CD38 monoclonal antibodies (daratumumab, isatuximab) 1432. Real-world evidence confirms this: among Medicare patients, median overall survival improved from 20.0 months (2000–2004) to 27.9 months (2005–2009) following the introduction of novel agents 14.
In China, annual percentage change in incidence was +3.28% from 2006 to 2014, moderating slightly to +2.32% from 2014 to 2016 10. Mortality increased at +0.78% annually from 2006 to 2014, then stabilized (APC: +0.34%, 2014–2016), suggesting emerging treatment impact 10. ARIMA projections indicate that China and the Russian Federation will experience continued ASIR increases through 2036, while England, France, and the United States are expected to achieve stabilization 1. Long-range forecasts to 2045 project that, absent changes in age-specific rates, global MM incidence and mortality will increase by 71% and 79%, respectively, driven primarily by demographic aging 6.
In Europe, patterns are heterogeneous but broadly stable in age-adjusted terms. In Switzerland, absolute case numbers increased from 419 to 557 per year between 1994–1998 and 2009–2013, but the age-adjusted incidence rate remained stable at 4.7–5.0 per 100,000, attributing the absolute rise to population aging alone 23. In Italy, ASIR showed only a modest annual rate of change (+0.28; 95% UI: −0.20 to +0.91) from 1990 to 2023, while the mortality-to-incidence ratio improved from 68.0% to 55.1%, reflecting better survival outcomes; notably, northern regions demonstrated greater ASMR improvement than southern regions, highlighting subnational disparities in treatment access 27.
3. Demographic Stratification: Age, Sex, and Race/Ethnicity
Age: MM is predominantly a disease of older adults. In the United States, the median age at diagnosis is 69 years, with 32.7% of cases occurring in the 65–74 age group and 24.9% in the 75–84 age group 24. Globally, age-specific incidence rates increase monotonically with age, exceeding 20 per 100,000 in the 85+ group in high-SDI regions 5. The highest age-specific mortality occurs in the 85–89 age group across all countries studied, with rates exceeding 20 per 100,000 in developed nations 1.
Sex: Males consistently experience 1.5- to 2-fold higher MM incidence and mortality than females across all regions. In the United States, age-adjusted incidence is 9.1 per 100,000 in males versus 6.1 per 100,000 in females 24. In Germany, age-standardized rates are 5.5 (males) versus 3.7 (females) per 100,000 26. Global age-standardized incidence was 2.12 per 100,000 in males versus 1.43 per 100,000 in females in 2021 2.
Race/Ethnicity: The most striking disparities are documented in the United States. Non-Hispanic Black (NHB) individuals carry a disproportionate burden, with MM incidence reaching 17.9 per 100,000 in Black males and 13.4 per 100,000 in Black females—approximately 2.3-fold higher than non-Hispanic White (NHW) rates 2418. Black individuals are diagnosed younger, with 35.3% presenting before age 60 versus only 16.5% of White patients, and exhibit higher disease burden at diagnosis including greater rates of extramedullary disease (incidence rate ratio: 1.39) 29. Mortality rate ratios comparing Black to White populations peaked at 2.77 in the 55–59 age group 3. Asian/Pacific Islander populations have the lowest incidence (~3.56–4.91 per 100,000) and lowest mortality of all US racial groups 318.
The following table summarizes US racial disparities in age-adjusted rates:
| Race/Ethnicity | Incidence (per 100,000) | Mortality (per 100,000) |
|---|---|---|
| Non-Hispanic Black | 17.43 (17.9 male, 13.4 female) | 9.12 |
| Hispanic | 8.28 | Variable |
| Non-Hispanic White | ~8.4 (M), ~5.2 (F) | ~4.4 |
| Asian/Pacific Islander | 4.91 | 1.89 |
Importantly, survival improvements with novel therapies have not been distributed equally. Patients aged ≥75 years showed minimal improvement in 10-year relative survival rates (7.8% to 9.3%), and among NHB patients aged 65–74 years, 10-year survival gains did not reach statistical significance, contrasting with marked improvements in NHW and Hispanic patients 9.
4. Risk-Factor and Precursor-State Stratification
Monoclonal Gammopathy of Undetermined Significance (MGUS): Nearly all MM cases are preceded by MGUS. In the US general population over age 50, MGUS prevalence is approximately 3% 31. In high-risk populations—Black individuals and those with a family history of hematologic malignancy—MGUS prevalence reaches 9–15% by conventional serum protein electrophoresis, and up to 13% by high-sensitivity mass spectrometry 30.
Age-specific MGUS incidence rates in NHW populations are 52, 86, 142, and 181 per 100,000 person-years at ages 50, 60, 70, and 80 years, respectively; NHB populations demonstrate rates approximately double at each stratum: 110, 212, 392, and 570 per 100,000 person-years 8. The cumulative risk of developing MGUS between ages 50 and 85 is 2.8% for NHW and 6.1% for NHB individuals 8. Critically, mathematical modeling demonstrates that the excess MM incidence in Black populations is explained entirely by higher MGUS incidence rather than accelerated MGUS-to-MM progression rates—progression rates are uniform across racial groups—pointing upstream to differences in MGUS development as the mechanistic driver 11.
The average preclinical duration from MGUS to MM diagnosis is 20.5 years (95% CI: 16.5–26.1) for NHW and 14.2 years (95% CI: 11.5–17.6) for NHB populations 8. Among patients with MGUS, the risk of progression to multiple myeloma or related disorders is approximately 1% per year, although progression risk varies substantially according to baseline risk factors such as M-protein level and free light-chain ratio 31. A baseline M-protein level ≥1.5 g/dL strongly predicts progression (hazard ratio: 5.51) 31.
Obesity and other modifiable risk factors: Obesity is the most significant modifiable risk factor for MM. In MGUS cohorts, overweight status (HR: 1.55) and obesity (HR: 1.98) independently predict progression to MM 13. Among individuals with normal baseline BMI, each additional year of cumulative excess body mass index exposure increases progression risk by approximately 21% 31. In a high-risk MM screening cohort, individuals with BMI ≥30 kg/m² had 73% higher odds of MGUS detection (OR: 1.73) 30. Additional modifiable risk factors include heavy smoking (>30 pack-years; OR: 2.19), short sleep duration (<6 hours/day; OR: 2.11), and sedentary behavior; conversely, high physical activity was associated with decreased MGUS likelihood (OR: 0.45) 30. In China, 5.5% of MM deaths in 2021 were attributed to high body mass index, identifying obesity as an important population-attributable risk factor 4.
5. Disease Burden: Mortality, DALYs, and Quality of Life
Global DALYs from MM totaled 2,595,595 in 2021, a 131% increase since 1990 28. In Italy, where subnational DALY data are available, MM generated 73,600 DALYs in 2023, of which 93.4% derived from years of life lost (YLLs), emphasizing the mortality-dominated burden 27. High-SDI regions bear the greatest absolute DALY burden, though middle-SDI regions exhibit the most rapid DALY growth (AAPC: >2% annually) 22.
Patient-reported health-related quality of life (HRQoL) is substantially impaired across disease phases. In a multi-centre UK study of 557 MM patients (mean age 68.4 years), patients reported a mean of 7.2 symptoms, with fatigue (87.6%), pain (71.5%), and breathlessness (60.8%) being most prevalent and burdensome 20. Global health status (EORTC QLQ-C30) had a mean score of 61.2 (SD: 22.3), and EuroQol 5D Index was 0.65 (SD: 0.28) 20. Importantly, disease-stage markers such as ISS did not independently predict HRQoL when symptom burden and functional status were accounted for, underscoring the primacy of patient-reported outcomes in clinical monitoring 20. Modern triplet induction regimens—particularly lenalidomide-bortezomib-dexamethasone (RVd)—demonstrated statistically significant improvements in FACT-MM and EQ-5D scores compared to older doublet or melphalan-based regimens in real-world practice 21.
Survival disparities by sociodemographic status are substantial. In younger US patients (<65 years), 4-year overall survival declined from 71.1% (no adverse factors) to 46.5% (3 adverse factors: unmarried, uninsured/Medicaid, low income) 12. After adjustment for sociodemographic factors, race/ethnicity was not independently associated with survival, suggesting that healthcare access, insurance status, and socioeconomic position—rather than intrinsic biology—mediate much of the observed racial survival gap 12.
6. Interpretive Synthesis for Medical Professionals
The epidemiologic landscape of MM presents several clinically actionable insights. First, the aging global population and the disease's exponential age-specific risk mandate heightened diagnostic vigilance in patients over 60 years presenting with unexplained anemia, bone pain, hypercalcemia, or renal dysfunction—classic "CRAB" criteria. Second, the substantially higher burden in Black populations, beginning with elevated MGUS prevalence at younger ages, may support further evaluation of targeted MGUS screening strategies in high-risk populations and those with family history of hematologic malignancy, particularly as mass spectrometry-based detection can identify monoclonal proteins below traditional electrophoresis thresholds 30.
Third, obesity is a modifiable upstream risk factor that clinicians can address in MGUS patients to potentially slow progression. Weight management counseling should be integrated into the routine management of patients with established MGUS. Fourth, the divergence in mortality trends between high-SDI and low-to-middle-SDI regions underscores the central role of treatment access in determining population-level outcomes. As novel therapies—including quadruplet induction with daratumumab-VRd, BCMA-targeted CAR-T therapies, and bispecific antibodies—continue to improve clinical outcomes for selected patients in high-income settings, global health planning must prioritize equitable access to these agents 32.
Fifth, regional health systems facing rapidly rising MM burden—particularly China and the Russian Federation, where ASIR is projected to continue increasing through 2036—require investment in diagnostic infrastructure, hematology workforce capacity, and affordable access to proteasome inhibitors and immunomodulatory drugs as foundational therapies 14. Finally, the integration of systematic patient-reported outcome monitoring into clinical practice is supported by evidence that symptom burden and functional status are major contributors to quality of life beyond biomedical staging alone, and that identifying fatigue, pain, and psychological distress early enables targeted supportive interventions that meaningfully improve the patient experience across all phases of the disease 2021.