Randomized Phase II Study of Bortezomib, Lenalidomide, and Dexamethasone (VRD) Versus Lenalidomide and Dexamethasone (RD) in Elderly Patients with Newly Diagnosed Multiple Myeloma (KMM1910)

Purpose: While triplet regimens are considered optimal for treatment of multiple myeloma (MM), the benefit of adding bortezomib to lenalidomide and dexamethasone remains prospective-wise unclear in elderly patients due to frailty and potential toxicities. Materials and Methods: This multicenter, randomized phase II study evaluated the efficacy and safety of bortezomib/lenalidomide/dexamethasone (VRd) versus Rd (lenalidomide/ dexamethasone) in transplant-ineligible patients aged ≥ 70 years. Results: Forty-nine patients were randomized to receive either VRd or Rd. The overall response rates were comparable between two arms (72.7% for Rd and 84.6% for VRd, p=0.312). Although VRd achieved a significantly higher minimal residual disease negativity rate compared to Rd (76.9% vs. 12.5%, p=0.004), this deeper response did not translate into a statistically significant improvement in the primary endpoint, the 3-year progression-free survival rate, which was 53.8% for VRd and 45.5% for Rd (p=0.520). Similarly, no significant difference was observed in overall survival OS between the two arms. Safety analysis revealed that grade 3-4 adverse events were comparable, occurring in 73.1% of the VRd arm and 77.3% of the Rd arm. Notably, infections were a major cause of treatment discontinuation and mortality, accounting for seven deaths overall. Conclusion: While VRd induced numerically deeper responses, its clinical benefit in a real-world-representative elderly population may be limited by treatment tolerability and infection risks.