Surveillance of Smoldering Myeloma Patients Who Progress to Active Disease Is Associated with Favorable Outcomes

Smoldering multiple myeloma (SMM) is a precursor condition to active multiple myeloma (MM). While surveillance is standard, data on its effectiveness in preventing irreversible complications is limited.

We conducted a two-center matched retrospective cohort study comparing 57 patients who progressed from SMM (pSMM) with 57 de novo MM (dnMM) patients, matched by age and diagnosis year. Primary endpoints were end-organ damage and progression-free survival (PFS).

Median surveillance prior to progression in pSMM was 40 months. At active MM diagnosis, irreversible renal/bone complications were observed in 44% of pSMM patients compared with 72% of dnMM (p = 0.002). dnMM patients presented more frequently with hypercalcemia (12.3% vs. 1.8%, p = 0.03), lytic lesions (67% vs. 45%, p = 0.02), pathological fractures (31% vs. 10%, p = 0.008), and detrimental bone disease (58% vs. 25%, p < 0.001). ISS and R-ISS stages were higher in dnMM, while treatment patterns were similar. At 3 years, PFS was significantly higher in pSMM (59% vs. 30%, p = 0.01), as was overall survival (OS; 92% vs. 76%, p = 0.01). Clinical surveillance was associated with reduced disease burden, fewer irreversible complications, and improved PFS and OS compared with dnMM.

These findings support surveillance effectiveness and highlight the need to optimize follow-up strategies.