OA – 45: Subcutaneous Daratumumab Plus Lenalidomide Versus Lenalidomide Alone as Maintenance Therapy in Newly Diagnosed Multiple Myeloma After Transplant: Primary Results from the Phase 3 AURIGA Study

Introduction: Induction/consolidation (ind/con) with autologous stem cell transplant (ASCT) and lenalidomide (R) maintenance (maint) is standard of care (SoC) for transplant-eligible (TE) patients (pts) with newly diagnosed multiple myeloma (NDMM). Daratumumab (DARA) is a human anti-CD38 monoclonal antibody approved for ind/con treatment of TE NDMM. To date, no randomized trials have directly compared DARA-based therapy to SoC R maint therapy. Here we present the primary results of the phase 3 AURIGA study (NCT03901963) evaluating the addition of DARA to R maint in TE NDMM pts who were anti-CD38 naïve and positive (pos) for minimal residual disease (MRD) following ASCT after SoC ind/con.

Methods: Eligible pts with NDMM were aged 18-79 yrs, in ≥VGPR and MRD pos (10^–5; NGS) following ASCT, anti-CD38 naïve, received ≥4 ind cycles, and enrolled within 12 mos of start of ind therapy and 6 mos of ASCT. Pts were stratified by cytogenetic risk and randomized 1:1 to receive 28-day cycles of R maint (10mg PO D1-28 [after C3, 15mg PO, if tolerated]) ± subcutaneous DARA (DARA SC; 1,800mg QW C1-2, Q2W C3-6, Q4W C7+) for ≤36 cycles or until disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was MRD-negative (neg) conversion rate (10^–5) by 12 mos from start of maint therapy.

Results: 200 pts were randomized (D-R, n=99; R, n=101). Demographic characteristics were well balanced between arms: median age (yrs) was 63 for D-R and 62 for R, and 25.3% and 23.5% of pts had ISS stage III disease. At diagnosis, 23.9% of D-R and 16.9% of R pts had high cytogenetic risk (del17p/t[4;14]/t[14;16]). Pts received a median of 5 (range, 4-8) ind cycles in both groups prior to study entry. The MRD-neg (10^–5) conversion rate by 12 mos (primary endpoint) was 50.5% for D-R and 18.8% for R (odds ratio [OR], 4.51; 95% CI, 2.37-8.57; P < 0.0001) with a consistent benefit favoring D-R across all relevant subgroups. At median follow-up (32.3 mos), overall MRD-neg (10⁻⁵) rate was 60.6% for D-R and 27.7% for R. Complete response or better rate favored D-R (75.8% vs 61.4%; OR, 2.00; 95% CI, 1.08-3.69; P=0.0255). PFS favored D-R (HR, 0.53; 95% CI, 0.29-0.97); estimated 30-mo PFS rate was 82.7% for D-R and 66.4% for R.



D-R and R pts received a median of 33 and 21.5 maint cycles, respectively; 88.5% and 78.6% completed 12 cycles. Grade 3/4 treatment-emergent adverse events (TEAEs) occurred in 74.0% of D-R and 67.3% of R pts; infections (18.8% and 13.3%) and neutropenia (46.9% and 41.8%) were most common. Serious TEAEs occurred in 30.2% of D-R and 22.4% of R pts, and fatal TEAEs in 2.1% and 1.0%.


Conclusions: The addition of DARA to R maint in TE NDMM pts who were MRD pos and anti-CD38 naïve post-ASCT resulted in a significantly higher conversion rate to MRD neg by 12 mos of maint treatment than with R alone. PFS data are immature but favor D-R. No new safety signals were observed. These results demonstrate the benefit of adding DARA to R maint therapy.