The addition of bortezomib to lenalidomide and dexamethasone significantly improved both progression-free and overall survival with an acceptable risk-benefit profile in patients with newly diagnosed multiple myeloma who were not planning for immediate autologous hematopoietic stem cell transplantation (ASCT), a study published in the journal The Lancet has shown.1
The combination of bortezomib with lenalidomide and dexamethasone has demonstrated significant efficacy in newly diagnosed multiple myeloma. Therefore, researchers sought to evaluate whether adding bortezomib to lenalidomide and dexamethasone would improve outcomes in patients with previously untreated myeloma who were not planned for immediate ASCT.
For the open-label, phase 3 trial (ClinicalTrials.gov Identifier: NCT00644228), investigators enrolled 525 patients with newly diagnosed multiple myeloma and randomly assigned them 1:1 to receive either initial therapy with bortezomib, lenalidomide, and dexamethasone (VRd) or lenalidomide and dexamethasone alone (Rd).
Results showed that adding bortezomib to lenalidomide and dexamethasone significantly reduced the risk for progression or death by nearly 29% (hazard ratio [HR], 0.712; 96% CI, 0.56-0.906; P =.0018). Median progression-free survival was 43 months in the VRd group compared with 30 months in the Rd arm.
Researchers also found that treatment with bortezomib significantly reduced the risk of death by approximately 30% vs Rd alone (HR, 0.709; 95% CI, 0.524-0.959; P =.025). Median overall survival was 75 months and 64 months with VRd and Rd, respectively.
Eighty-two percent of patients in the VRd group achieved an overall response vs 72% in the Rd group, including 16% and 8% who achieved a complete response or better, respectively.
In the VRd arm, 82% of patients reported grade 3 or worse adverse events and 23% discontinued induction therapy due to adverse events. Three-quarters of patients in the Rd group experienced grade 3 or worse adverse events and 10% discontinued treatment as a result of adverse events.
Of note, 2 patients in the VRd died due to induction therapy, while no patients in the Rd group experienced treatment-related death.
1. Durie BGM, Hoering A, Abidi MH, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and
dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2016 Dec 22. doi: 10.1016/S0140-6736(16)31594-X. [Epub ahead of print]