MM-155: Phase 3 MAIA Study: Overall Survival (OS) Results with Daratumumab, Lenalidomide, and Dexamethasone (D-Rd) vs Lenalidomide and Dexamethasone (Rd) in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma (TIE-NDMM)

Abstract

Context Daratumumab plus standard-of-care (SOC) showed superior efficacy vs SOC for patients with TIE-NDMM (phase 3 ALCYONE, MAIA, and CASSIOPEIA; primary analyses). In ALCYONE, after longer follow-up, adding daratumumab to bortezomib, melphalan, and prednisone significantly reduced the risk of death by 40%. In MAIA (primary analysis), D-Rd reduced the risk of progression/death by 44% vs Rd (median follow-up, 28 months). Objective Updated efficacy and safety of D-Rd vs Rd from MAIA (NCT02252172; pre-specified interim OS analysis). Design Open-label, randomized, active-controlled. Patients Patients with TIE-NDMM were randomly assigned 1:1 to receive D-Rd (n=368) or Rd (n=369); median age: 73 years. Baseline characteristics were well balanced between arms. Interventions 28-day cycles of oral Rd (R: 25 mg QD [Days 1–21]; d: 40 mg [Days 1, 8, 15, 22]) ± IV daratumumab (16 mg/kg QW [Cycles 1–2], Q2W [Cycles 3–6], and Q4W thereafter) until progression or unacceptable toxicity. Main Outcome Measures Primary endpoint: progression-free survival (PFS); key secondary endpoints: overall response rate (ORR), OS, and safety. Results After a median follow-up of 56.2 months, the risk of death significantly reduced with D-Rd vs Rd; median OS: not reached (NR) in either arm (hazard ratio [HR], 0.68 [95% CI, 0.53–0.86]; P=0.0013). The median PFS was NR with D-Rd vs 34.4 months with Rd (HR, 0.53 [0.43–0.66]; P 15% incidence) grade 3 or 4 treatment-emergent adverse events with D-Rd/Rd were neutropenia (54.1%/37.0%), pneumonia (19.2%/10.7%), anemia (16.8%/21.6%), and lymphopenia (16.5%/11.2%). Conclusions After a median follow-up of ≈5 years, patients with TIE-NDMM had a significant and clinically meaningful OS improvement with D-Rd vs Rd. The significant PFS benefit of D-Rd was maintained, with a 47% reduction in the risk of progression/death. The favorable benefit-risk profile supports the use of D-Rd in patients with TIE-NDMM. Together with the OS benefit observed in ALCYONE, these results support using frontline daratumumab-based regimens to maximize PFS for optimal long-term outcomes.