Daratumumab with lenalidomide as maintenance after transplant in newly diagnosed multiple myeloma: the AURIGA study.

No randomized trial has directly compared daratumumab and lenalidomide (D-R) maintenance therapy versus standard-of-care lenalidomide (R) alone post-transplant. Here, we report the primary results of the phase 3 AURIGA study evaluating D-R versus R maintenance in NDMM patients who were in ≥very good partial response, minimal residual disease (MRD; threshold 10-5) positive, and anti-CD38 naïve post-transplant. Patients were randomized 1:1 to D-R or R maintenance for up to 36 cycles. Two hundred patients were randomized (D-R, n=99; R, n=101). The primary endpoint, MRD-negative (10-5) conversion rate by 12 months from start of maintenance, was significantly higher for D-R versus R (50.5% vs 18.8%; odds ratio [OR], 4.51; 95% confidence interval [CI], 2.37-8.57; P<0.0001). MRD-negative (10-6) conversion rate was similarly higher with D-R (23.2% vs 5.0%; OR, 5.97; 95% CI, 2.15-16.58; P=0.0002). At 32.3 months' median follow-up, D-R achieved a higher overall MRD-negative (10-5) conversion rate (D-R, 60.6% vs R, 27.7%; OR, 4.12; 95% CI, 2.26-7.52; P<0.0001) and ≥complete response rate (75.8% vs 61.4%; OR, 2.00; 95% CI, 1.08-3.69; P=0.0255) versus R alone. Progression-free survival (PFS) favored D-R versus R (hazard ratio, 0.53; 95% CI, 0.29-0.97); estimated 30-month PFS rates were 82.7% for D-R and 66.4% for R. Incidences of grade 3/4 cytopenias (54.2% vs 46.9%) and infections (18.8% vs 13.3%) were slightly higher with D-R versus R. In conclusion, D-R maintenance achieved a higher MRD-negative conversion rate and improved PFS post-transplant versus R alone, with no new safety concerns. This trial was registered at www.ClinicalTrials.gov: #NCT03901963.