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

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.

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 2 hematologists using a predefined hierarchical classification based on the underlying cause of death.

MM progression remained the leading cause of death but declined significantly across study periods, from 86.4% in 2008 to 2013 to 62.5% in 2020 to 2025 (P = .001). Conversely, non-MM-related deaths increased from 7.6% to 31.8%. Early deaths decreased significantly (28.8% vs. 9.1%; P = .004). Cardiovascular and infectious terminal events became more frequent, whereas multiorgan failure became less frequent.

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.