Abstract
SWOG S0777, a randomized phase III trial, compared bortezomib, lenalidomide and dexamethasone (VRd) with lenalidomide and dexamethasone (Rd). This updated analysis includes 460 patients evaluable for survival endpoints: 225 eligible and analyzable patients were randomized to Rd and 235 to VRd. The 6-month induction was six 28-day cycles of Rd and eight 21-day cycles of VRd followed by Rd maintenance for all patients. Median follow up is 84 months. Median PFS is 41 months for VRd and 29 months for Rd: stratified hazard ratio (96% Wald Confidence Interval) was 0.742 (0.594, 0.928) and one-sided stratified log-rank P-value 0.003. Median OS for VRd is still not reached with median OS for Rd being 69 months: stratified hazard ratio (96% Wald Confidence Interval) was 0.709 (0.543, 0.926) and stratified two-sided P-value was 0.0114. Both PFS and OS were improved with VRd versus Rd adjusting for age (P-values: 0.013 [PFS]; 0.033 [OS])). Median duration of Rd maintenance was 17.1 months. The addition of bortezomib to lenalidomide dexamethasone for induction therapy results in a statistically significant and clinically meaningful improvement in PFS as well as better OS. VRd continues to represent an appropriate standard of care irrespective of age.
Highlights
The combination of bortezomib, lenalidomide, and dexamethasone was selected at the time of trial design in 2007 to achieve the maximum response in the frontline setting for myeloma therapy
Patients and study design The SWOG S0777 randomized, open-label phase 3 trial was done at Southwest Oncology Group (SWOG) and National Clinical Trials (NCTN) member institutions as listed in the appendix
The baseline characteristics were wellbalanced between treatment groups
Summary
The combination of bortezomib, lenalidomide, and dexamethasone was selected at the time of trial design in 2007 to achieve the maximum response in the frontline setting for myeloma therapy. Both bortezomib and lenalidomide were at the time approved for use in the relapsed setting, but still under evaluation in patients with previously untreated multiple myeloma. Lenalidomide is an immunomodulatory agent which exhibits multifaceted, anti-myeloma activity by enhancing immune function, disrupting aberrant stromal cell support as well as having direct anti-myeloma cell effects[4,5,6,7]. Durie et al Blood Cancer Journal (2020)10:53 bortezomib and lenalidomide inhibit NF-κB and in combination demonstrate enhanced proapoptotic effects[8,9]. Prior to the current study, the VRd combination showed promising activity in both the relapsed and newly diagnosed settings[12,13,14]
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