Lenalidomide/Dexamethasone versus Bortezomib/Lenalidomide/Dexamethasone in Newly Diagnosed Multiple Myeloma: Results of the Phase 3 SWOG S0777 Trial
Lenalidomide with dexamethasone (Rd) is a standard of care for patients with previously untreated multiple myeloma (MM).1 Durie and colleagues2 reported on the results of SWOG S0777, a randomized phase 3 trial that assessed the benefit of the addition of bortezomib 1.3 mg to standard lenalidomide plus dexamethasone (VRd) in 525 previously untreated patients with MM without an intent for immediate autologous stem-cell transplantation. In this trial, induction therapy for Rd consisted of lenalidomide 25 mg/day and dexamethasone 40 mg/day; VRd consisted of lenalidomide 25 mg/day and dexamethasone 20 mg/day plus bortezomib 1.3 mg/m2. Induction therapy was followed by Rd maintenance for all patients until progression, unacceptable toxicity, or withdrawal of consent. The primary study end point was progression-free survival (PFS); secondary end points were overall response rate (ORR), overall survival (OS), and safety. The results showed that PFS was significantly improved with VRd compared with Rd therapy (hazard ratio [HR], 0.712; P = .0018); median PFS was 43 months versus 30 months. This also translated into a significant improvement in OS (HR, 0.709; P = .0125), with a 30% decrease in the risk of death with VRd versus Rd; median OS was 75 months for VRd versus 64 months. ORR (? partial response [PR]) was 81.5% for VRd and 71.5% for Rd, including a complete response (CR) rate of 15.7% and 8.4%, respectively, and a very good partial response (VGPR) of 27.8% and 23.4%, respectively. The safety profile was similar between the 2 treatment arms, with the exception of more frequent grade 3/4 neuropathy with VRd (24% vs 5%; P <.0001), as expected. The most common grade 3/4 hematologic adverse events (AEs) were anemia (13% vs 16%), leukopenia (14% vs 16%), lymphopenia (23% vs 18%), neutropenia (19% vs 21%), and thrombocytopenia (18% vs 14%). The most common nonhematologic grade 3/4 AEs were fatigue (30%), sensory neuropathy (26%), hyperglycemia (18%), thrombosis/embolism (17%), hypokalemia (15%), muscle weakness (11%), diarrhea (10%), and dehydration (10%). In conclusion, the addition of bortezomib to standard induction therapy of Rd regimen in patients with previously untreated MM resulted in significant improvement in survival outcomes, while showing an acceptable safety and tolerability profile.
- National Comprehensive Cancer Network (NCCN). Multiple Myeloma. 2015.
- Durie B, et al. ASH 2015. Abstract 25.