SWOG S0777 Trial

Background

SWOG S0777: phase III RCT randomizing 525 transplant-deferred or transplant-ineligible patients with newly diagnosed multiple myeloma to triplet RVD vs doublet Rd induction.

Interventions and follow up

Arm A: VRd Q21D x C1-8, then Rd maintenance
Arm B: Rd Q28D x C1-6, then Rd maintenance
Primary endpoint: PFS
mFollow up: 55mo

Results

mPFS: 43mo (Arm A) vs 30mo (Arm B); HR 0.71, 95% CI 0.56–0.91, P=.0018
mPFS (updated, ITT): 41mo vs 29mo; HR 0.742, 95% CI 0.594–0.928, P=.003
mOS: 75mo vs 64mo; HR 0.709, 95% CI 0.524–0.959, P=.0125
DoS (duration of survival, updated): 50mo vs 39mo; P=.0175

Adverse events

Grade ≥3 neurologic toxicity (Arm A vs B): 33% vs 11%; P<.0001 (peripheral neuropathy)
Second primary cancers: 4% in each group; GI events more frequent with RVD; treatment-related deaths rare in both arms

Conclusions

Triplet RVD induction significantly improved progression-free and overall survival vs doublet Rd in newly diagnosed MM not slated for immediate transplant, establishing RVD as a standard induction regimen.

Key Limitations

Used 21-day bortezomib dosing with twice-weekly IV administration, driving high neuropathy rates; modern weekly subcutaneous bortezomib is better tolerated. Predates daratumumab-based quadruplet induction. Median age 63; older/frail patients underrepresented.

Clinical Context

Established RVD as a standard frontline triplet for NDMM regardless of immediate transplant intent; endorsed by ESMO and ASCO. (Regimen: bortezomib 1.3 mg/m2 IV D1,4,8,11; lenalidomide 25 mg D1–14; dexamethasone 20 mg D1,2,4,5,8,9,11,12 Q21D x8; then Rd maintenance lenalidomide 25 mg D1–21 plus dexamethasone 40 mg weekly Q28D.)

References