Induction therapy followed by high-dose therapy with autologous stem-cell transplant (ASCT) is a highly effective treatment for transplant–eligible patients with newly diagnosed multiple myeloma (NDMM). However, this treatment is not curative and most patients will experience disease progression. Lenalidomide maintenance after ASCT showed improved progression-free survival (PFS) in several trials, but these trials were not powered to demonstrate overall survival (OS) benefit. In addition, some patients receiving lenalidomide maintenance developed second primary malignancy (SPM). A recent meta-analysis, conducted at the request of the US Food and Drug Administration (FDA), examined the impact of lenalidomide maintenance therapy following ASCT in 1208 patients with NDMM across three randomized controlled trials (CALGB 100104, IFM 05-02, and GIMEMA) to determine the impact of this approach on survival and safety.
According to results from this analysis, lenalidomide maintenance was associated with an impressive 29.3 month improvement in median PFS compared to placebo or observation (52.8 months vs 23.5 months; HR 0.48). In addition, at a median follow-up of 79.5 months, the OS had not been reached in the lenalidomide maintenance arm, compared to 86.0 months in the placebo or observation arm (HR 0.75, P = .001). The seven-year survival rate was 62% with lenalidomide maintenance compared to 50% with placebo or observation. The OS and PFS benefit of lenalidomide was consistent across all patient subgroups except for patients with International Staging System (ISS) disease stage III. The most favorable OS benefit was observed in patients who received a lenalidomide-based induction therapy. Furthermore, lenalidomide maintenance resulted in a 28% reduction in risk of progression or death on second-line therapy (PFS2).
Treatment-related adverse events (AEs) occurred more frequently in the lenalidomide maintenance arm, where 29.1% of patients discontinued therapy due to AEs (compared to 12.2% with placebo). Incidence of SPM before disease progression was higher in patients receiving lenalidomide maintenance (hematologic: 5.3% vs 0.8%; solid tumor: 5.8% vs 2.0%). However, incidence of progression and death from myeloma were higher in the group that did not receive maintenance.
In their conclusion, the authors indicated that based on the consistent, clinically meaningful OS and PFS benefit with lenalidomide maintenance after ASCT across the three trials, this approach can be considered standard of care in patients with NDMM. They also commented that cost of maintenance therapy should be weighed against the costs of shorter survival, earlier progression, and earlier use of subsequent lines of therapies in patients who did not receive maintenance.