The future mortality trends in multiple myeloma (SEER analysis 2000–2030).

7550 Background: Novel therapies have transformed Multiple Myeloma (MM) from a rapidly fatal diagnosis into a chronic condition. However, this extended survival exposes patients to a new set of competing risks. We utilized the SEER database to quantify the evolving burden of cause-specific mortality in the modern era and project future mortality trends. Methods: We identified 129,837 patients diagnosed with MM from 2000–2022 using SEER-17 registries. Patients were stratified by era: Pre-Novel (2000–06), Early-Novel (2007–14), and Modern (2015+). Median overall survival (mOS) and cumulative incidence function of death (CIF) were analyzed using Kaplan-Meier estimates and Gray’s test, respectively. Fine-Gray competing risk regression was used to estimate sub-distribution hazard ratios (sHR) for non-cancer death. Non-cancer mortality burden was projected from 2021-2030 using linear regression models based on 2010–2021 trends. Results: Median Overall Survival (mOS) improved from 32 months (Pre-Novel era) to 49 months (Early-Novel era) and 63 months (Modern era) (p<0.001). Modern-era patients had lower odds of dying from MM compared to the Pre-Novel era (OR 0.68, 95% CI 0.66–0.71, p<0.001). The 5-year CIF of MM-specific death decreased from 46.5% (Pre-Novel) to 28.0% (Modern) while the non-cancer death remained stable (20.2% vs 20.7%). Among 82,585 total deaths recorded, Myeloma remained the primary cause (62.5%), while non-cancer causes accounted for 37.5%. Cardiovascular disease was the most common specific non-cancer cause, accounting for 11.4% (n=9,383) of all deaths. Early decedents (<3 years) had significantly higher odds of dying from Myeloma compared to late survivors (65.1% vs 58.5%; OR 1.32, p<0.001). In contrast, late survivors (≥3 years) had significantly higher odds of death from cardiovascular disease (OR 1.16, 95% CI 1.11–1.21, p<0.001) and Infections (OR 1.16, 95% CI 1.05–1.28, p=0.003) as compared to early decedents. In Fine-Gray competing risk models, the modern era was associated with a reduced relative hazard of non-cancer death (sHR 0.80, p<0.001). The population of MM is projected to grow by 34.5% (from ~47,200 to ~63,500) between 2022 and 2030 and annual Myeloma-specific deaths are projected to increase by 6.1% (~2,980) by 2030, annual non-Cancer deaths are projected to rise by 38.8% (~3,600). Conclusions: Novel therapies have nearly doubled median survival in MM, narrowing the "mortality gap" as non-cancer causes as now approach half of annual deaths. Despite reduced relative hazards, the absolute non-cancer burden is projected to rise 49% by 2030. This necessitates the need for comprehensive survivorship care for the management of MM.