Slowing Mortality Improvements in Multiple Myeloma Despite Novel Therapies: Global Disparities by Sociodemographic Index, 1990-2023.

Background Despite major therapeutic advances in multiple myeloma, including proteasome inhibitors, immunomodulatory drugs, anti-CD38 monoclonal antibodies, and, more recently, B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell therapies and bispecific antibodies, the extent to which these innovations have translated into population-level mortality benefits remains unclear. Previous evidence is insufficient, as most studies are limited to high-income settings or clinical trials and lack global analyses stratified by the sociodemographic index (SDI), limiting the understanding of equitable real-world impact across diverse resource settings. Aim This study was designed using the specific, measurable, achievable, relevant, and time-bound (SMART) framework and aimed to (1) quantify global and SDI-stratified trends in multiple myeloma incidence and mortality from 1990 to 2023; (2) examine changes in age-standardized mortality rates before and after 2015, coinciding with the wider adoption of novel therapies; and (3) identify persistent disparities and propose actionable strategies to improve equitable access by 2030. Methods Incidence and mortality data were extracted from the Global Burden of Disease 2023 Results Tool, including 95% uncertainty intervals. Absolute numbers and age-standardized rates per 100,000 population were analyzed globally and across SDI quintiles from 1990 to 2023, with trends compared before and after 2015 to evaluate the population-level impact of novel therapies. Results Globally, multiple myeloma deaths increased by 157%, from 48,658 in 1990 to 125,087 in 2023, while incident cases rose by 191%, from 60,975 to 177,776, largely reflecting population growth and aging. The age-standardized death rate (ASDR) increased modestly from 0.91 to 1.55 per 100,000 over the full study period. Joinpoint regression analysis demonstrated modest improvement in age-standardized mortality rates in earlier decades (pre-2015 average annual percentage change (AAPC): -0.8%, 95% CI: -1.2 to -0.4, p < 0.05), but this trend slowed or plateaued after 2015 (post-2015 AAPC: +0.3%, 95% CI: -0.2 to +0.8, p > 0.05), despite the widespread adoption of novel immunotherapies. In 2023, the ASDR remained substantially higher in high-SDI countries (3.18 per 100,000) than in low-SDI countries (0.60 per 100,000). Middle- and low-SDI regions showed faster increases in incidence but more limited reductions in mortality. Conclusions The global burden of multiple myeloma continues to rise substantially. Although novel therapies have improved individual outcomes, the rate of mortality improvement has slowed since 2015. Persistent and marked disparities by SDI indicate that recent therapeutic advances, including BCMA-directed therapies, have not been equitably translated into population-level survival benefits, particularly in resource-limited settings. These findings highlight the urgent need for earlier diagnosis, improved access to modern therapies, and targeted health policies to reduce global inequities in multiple myeloma outcomes.