Early Lenalidomide and Dexamethasone Improve Survival in Certain High-Risk Patients With Smoldering Multiple Myeloma

Investigators in Spain have demonstrated that a regimen of lenalidomide and dexamethasone reduces the risk of disease progression and improves survival in patients with high-risk smoldering multiple myeloma.

The standard course of action for patients with smoldering multiple myeloma is watchful waiting. With a grant from Celgene, investigators in Spain conducted a phase III trial in 119 high-risk patients with multiple myeloma to test outcomes in 57 patients receiving a regimen of lenalidomide and dexamethasone versus 62 patients receiving no treatment.

Watchful waiting is a sensible strategy in most patients because the risk of progression is only about 10% per year. Most of these progressions occur in a high-risk group comprising 40% of all patients with smoldering multiple myeloma.

Finding high-risk patients involves measuring plasma cells that have infiltrated into bone marrow, evaluating bone marrow cells for irregular structural appearance, and identifying abnormalities in immunoglobulin levels. The results of this study do not apply to patients with hypercalcemia, bone lesions, renal failure, or anemia because none of the participants in this trial had these features.

Investigators measured the time to disease progression, the response rate, the overall survival rate, and the incidence of adverse events over the median 40-month follow-up period. Patients with high-risk smoldering multiple myeloma receiving the new regimen had an 85% probability of experiencing progression later than patients receiving no treatment (P <.001), a 76% probability of living longer than patients receiving no treatment (P = .03), and a higher 3-year survival rate than patients who did not receive treatment (94% versus 80%; P = .03).

Grade-3 adverse events in patients undergoing treatment included infection, asthenia, neutropenia, and rash, each occurring in ≤6% of patients. Although rashes occurred in 32% of patients, the majority of rashes were grade-1 adverse events (low severity). More concerning, deep-vein thrombosis occurred in 3 patients receiving treatment despite the fact that 2 of those patients were taking aspirin or an oral anticoagulant. Because patients with smoldering multiple myeloma are generally asymptomatic, any intervention should carry a low risk of adverse events.

Despite these drawbacks, treatment with lenalidomide and dexamethasone in patients with high-risk smoldering multiple myeloma has, for the first time, shown a significant benefit in reducing the risk of disease progression and improving survival.