Clinical Characteristics and Prognostic Analysis of Extramedullary Disease in Multiple Myeloma: A 15-Year Retrospective Cohort Study.

BACKGROUND

Extramedullary disease (EMD) in multiple myeloma (MM) is associated with poor prognosis, yet the clinical distinctions between bone-related EMD (bEMD) and soft tissue-associated EMD (sEMD) remain incompletely characterized. This study aimed to compare the clinical features and outcomes of bEMD versus sEMD and to develop a simple pre-treatment risk stratification tool using baseline clinical parameters.

METHODS

We retrospectively analyzed 118 patients with MM and EMD treated at a single center from 2011 to 2025, including 72 bEMD and 46 sEMD cases. Baseline characteristics, laboratory parameters, cytogenetic abnormalities, and survival outcomes were compared.

RESULTS

Patients with sEMD had significantly higher serum β2-microglobulin (β2-MG) levels (6.4 mg/L vs. 4.5 mg/L, p = 0.007) and a higher proportion of relapsed/refractory disease (41.3% vs. 15.3%, p = 0.002) compared to bEMD. Median progression-free survival (PFS) and overall survival (OS) were markedly shorter in patients with sEMD than in those with bEMD (PFS: 12.0 vs. 29.0 months, p < 0.001; OS: 25.0 vs. 67.0 months, p = 0.009). Multivariate analysis identified thrombocytopenia (PLT < 100 × 109/L), elevated β2-MG, multisite extramedullary involvement, and TP53 deletion as independent adverse prognostic factors. A risk scoring system incorporating β2-MG (0-2 points), thrombocytopenia (1 point), and multisite involvement (1 point) stratified patients into low-risk (0-2 points) and high-risk (3-4 points) groups with significantly different PFS (27.0 vs. 10.0 months, p < 0.001) and OS (54.0 vs. 22.0 months, p = 0.008).

CONCLUSIONS

sEMD represents a more aggressive subtype of MM with inferior outcomes. The proposed risk score, based on routinely available clinical parameters, effectively identifies high-risk patients at initial diagnosis and may guide individualized treatment strategies.