Changing Patterns of Causes of Death in Patients With Multiple Myeloma During the Modern Therapeutic Era

Background Therapeutic advances have substantially prolonged survival in multiple myeloma (MM). However, real-world evidence on temporal changes in causes of death remains limited. This study evaluated how mortality patterns have evolved during the era of novel therapies. Methods We conducted a retrospective real-world cohort study including 469 consecutive patients with MM managed at a tertiary referral center between 2000 and 2025. The primary analysis included 230 patients who died between 2008 and 2025. Causes of death were independently adjudicated by two hematologists using a predefined hierarchical classification based on the underlying cause of death. Results MM progression remained the leading cause of death but declined significantly across study periods, from 86.4% in 2008–2013 to 62.5% in 2020–2025 (P = 0.001). Conversely, non–MM-related deaths increased from 7.6% to 31.8%. Early deaths decreased significantly (28.8% vs. 9.1%; P = 0.004). Cardiovascular and infectious terminal events became more frequent, whereas multiorgan failure became less frequent. Conclusions The distribution of causes of death among deceased patients with MM has changed over time, with a declining proportion of deaths due to disease progression and an increasing contribution of competing non-MM causes. As survival improves, these findings support integrating cardiovascular care, infection prevention, and long-term management of comorbidities into MM survivorship strategies.