Observation is currently regarded as the standard of care for patients with smoldering multiple myeloma (SMM). Investigators designed a phase 3 trial to assess whether high-risk patients could benefit from early intervention.
In the trial, 125 patients were enrolled and randomized; 119 comprised the per-protocol population and were randomly assigned to receive either lenalidomide plus dexamethasone (n = 57) or observation (n = 62). The high-risk population was defined by the presence of both clonal plasma-cell and M-protein levels. Patients in the treatment group received nine 4-week induction cycles of lenalidomide plus dexamethasone, followed by maintenance lenalidomide therapy. The primary end point was time to progression, whereas the secondary end points were overall survival (OS), response rate, and safety.
Progression to MM occurred in 86% of patients in the observation arm compared with 39% in the lenalidomide-dexamethasone arm. Median OS has not been reached in either group, but 82% and 64% of patients remain alive at 75 months in the early treatment and observation arms, representing a 57% reduction in the risk of death for early treatment with lenalidomide-dexamethasone versus no treatment (hazard ratio, 0.43; 95% confidence interval, 0.2-0.9; P = 0.02). Rescue therapy was given to patients in both arms who failed initial therapy. Most patients responded to rescue treatments in both groups, resulting in 17 (77%) of 22 patients achieving an overall response in the treatment group and 45 (85%) of 53 patients achieving an overall response in the observation group.
Study investigators concluded that early treatment with lenalidomide-dexamethasone for high-risk SMM translates into a significant benefit in terms of patient outcomes. Furthermore, early exposure to lenalidomide-dexamethasone does not induce more resistant relapses.
Mateos M-V, et al. ASH 2016. Abstract 3308.