Global MM incidence in AYA increased 60% (1990-2021), with males experiencing 43% higher rates and widening health inequalities. 2. Middle SDI regions show the steepest burden increases (prevalence EAPC: 3.50%), requiring enhanced diagnostic capacity and treatment access. Multiple myeloma (MM) research has predominantly focused on elderly populations, leaving the burden among adolescents and young adults (AYA, aged 15-39 years) incompletely characterized. This study utilized Global Burden of Disease Study 2021 (GBD 2021) data to comprehensively assess global trends in MM burden among AYA from 1990 to 2021. We analyzed age-standardized incidence, mortality, and disability-adjusted life years (DALY) rates across genders, regions, and sociodemographic index (SDI) levels. Temporal trends were quantified using estimated annual percentage change (EAPC). Decomposition analysis identified drivers of burden changes, while inequality was assessed using slope index of inequality (SII) and concentration index. Future projections were generated using the Nordpred model. From 1990 to 2021, global age-standardized incidence rates increased 60% (from 0.05 to 0.08 per 100,000), with incident cases more than doubling from 1,013 to 2,537. Males experienced 43% higher incidence than females. Middle SDI regions showed the most pronounced prevalence increases (EAPC: 3.50%, 95% CI: 3.31-3.69), while high SDI regions exhibited declining mortality (EAPC: -0.15%, 95% CI: -0.25 to -0.06) and DALY rates (EAPC: -0.08%, 95% CI: -0.17 to 0.01). Epidemiological changes drove 47.93% of global DALY increases. Health inequalities worsened for males (SII increased from 2 to 3) but improved for females (SII decreased from 2 to 1). Projections indicate continued burden increases through 2040, particularly among males. MM burden among AYA increased substantially with marked heterogeneity across genders and SDI regions, necessitating targeted prevention strategies and enhanced care access, particularly in middle SDI regions and male populations.
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