Background
Phase 3, open-label, randomized controlled trial. N=200 patients with newly diagnosed transplant-eligible multiple myeloma who achieved ≥VGPR but were MRD-positive (10⁻⁵ by next-generation sequencing) following induction and autologous stem-cell transplantation. Patients with MRD-negative status post-ASCT were excluded. Multiple prior induction regimens permitted.
Interventions and follow up
Arm A (D-R): Daratumumab 1800 mg SC (weekly x 8 doses, then every 2 weeks x 8 doses, then monthly) + lenalidomide 10 mg PO (days 1–21 q28d), up to 36 maintenance cycles.
Arm B (R): Lenalidomide 10 mg PO (days 1–21 q28d), up to 36 maintenance cycles.
Primary endpoint: MRD-negativity conversion rate (10⁻⁵) at 12 months from start of maintenance
Median follow-up: 32.3 months
Arm B (R): Lenalidomide 10 mg PO (days 1–21 q28d), up to 36 maintenance cycles.
Primary endpoint: MRD-negativity conversion rate (10⁻⁵) at 12 months from start of maintenance
Median follow-up: 32.3 months
Results
MRD-negativity (10⁻⁵) at 12 mo: 50.5% vs 18.8%, OR 4.51 (95% CI 2.37–8.57), P<.0001
30-mo PFS rate: 82.7% vs 66.4%, HR 0.53 (95% CI 0.29–0.97)
≥CR rate at 12 mo: Substantially improved in D-R arm vs R arm
30-mo PFS rate: 82.7% vs 66.4%, HR 0.53 (95% CI 0.29–0.97)
≥CR rate at 12 mo: Substantially improved in D-R arm vs R arm
Adverse events
Hematologic (D-R vs R): Grade ≥3 neutropenia 53.3% vs 40.5%.
Infection: Grade ≥3 infections 13.3% vs 6.1%.
Administration: Infusion/injection reactions any grade 11.0%; no grade ≥3 injection-site reactions. No new safety signals identified.
Infection: Grade ≥3 infections 13.3% vs 6.1%.
Administration: Infusion/injection reactions any grade 11.0%; no grade ≥3 injection-site reactions. No new safety signals identified.
Conclusions
Daratumumab added to lenalidomide maintenance significantly improved MRD-negative conversion in post-ASCT NDMM patients with residual MRD-positive disease, with an early PFS benefit, supporting D-R as a biologically rational intensification strategy for MRD-positive patients after ASCT.
Key Limitations
The trial enrolled exclusively MRD-positive patients, limiting applicability to patients who achieve MRD-negativity post-ASCT (the majority). The sample size (N=200) was modest, limiting power for PFS and OS analyses. MRD testing methodology was not uniform across sites. Different induction regimens were permitted, introducing heterogeneity. Whether MRD-negative conversion translates into durable PFS or OS benefit at longer follow-up remains to be established.
Clinical Context
AURIGA supports risk-adapted, MRD-guided intensification of maintenance therapy. Combined with GRIFFIN and CASSIOPEIA, daratumumab-based therapy is endorsed by ASCO and ESMO guidelines for transplant-eligible NDMM. This trial specifically addresses the high-risk subgroup of MRD-positive patients, where additional intervention has the greatest potential benefit.