OAB-001: Overall survival and progression-free survival by treatment duration with Daratumumab + Lenalidomide/Dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: phase 3 MAIA study

Introduction

In the primary analysis of MAIA, daratumumab (DARA) plus lenalidomide and dexamethasone (D-Rd) reduced the risk of disease progression or death by 44% vs lenalidomide and dexamethasone (Rd) in transplant-ineligible patients (pts) with newly diagnosed multiple myeloma (NDMM). Here, we report the updated efficacy and safety of D-Rd vs Rd after almost 5 years of median follow-up from the prespecified interim overall survival (OS) analysis of MAIA (NCT02252172).

Methods

Pts with NDMM ineligible for high-dose chemotherapy and autologous stem cell transplantation due to age ≥65 years or comorbidities were randomized 1:1 to D-Rd or Rd. All pts received 28-day cycles of Rd (R: 25 mg PO once daily on Days 1-21; d: 40 mg PO on Days 1, 8, 15, 22) ± DARA (16 mg/kg IV QW for Cycles 1-2, Q2W for Cycles 3-6, and Q4W thereafter). All pts were treated until disease progression/unacceptable safety events. The primary endpoint was progression-free survival (PFS).

Results

737 pts (D-Rd, 368; Rd, 369) enrolled and baseline characteristics were well balanced. Median age was 73 (range, 45-90) years. At a 56.2-month median follow-up, a significant 32% reduction in the risk of death was observed with D-Rd vs Rd. Median OS was not reached (NR) in either arm (HR, 0.68; 95% CI, 0.53-0.86; P=0.0013 [crossing the prespecified stopping boundary of P=0.0414]); estimated 5-year OS rates were 66.3% with D-Rd and 53.1% with Rd. The updated median PFS was NR with D-Rd vs 34.4 months with Rd (HR, 0.53; 95% CI, 0.43-0.66; PPP=0.2480); a PFS benefit was not observed with D-Rd vs Rd in pts who received P=0.3579). No new safety concerns were identified with longer follow-up. The most common grade 3/4 treatment-emergent adverse event was neutropenia (D-Rd, 54.1%; Rd, 37.0%).

Conclusions

After ~5 years of follow-up, D-Rd vs Rd showed a significant and clinically meaningful PFS and OS improvement in transplant-ineligible pts with NDMM. Additionally, D-Rd showed a greater PFS benefit vs Rd among pts treated for ≥18 months than among pts treated for shorter durations. Taken together with real-world data indicating that many transplant-ineligible pts do not receive a second line of therapy, the favorable benefit-risk profile observed in MAIA supports the frontline use of D-Rd in transplant-ineligible pts with NDMM.