New Indication: Daratumumab for High-Risk Smoldering Myeloma

Phase 3, open-label, multicenter, randomized trial (AQUILA)

Patients with high-risk smoldering multiple myeloma without end-organ damage

Daratumumab subcutaneous monotherapy vs. active monitoring

PFS @ 5 yrs: 63.1% vs. 40.8% (HR: 0.49 [0.36–0.67])

OS @ 5 yrs: 93.0% vs. 86.9% (HR: 0.52 [0.27–0.98])

CR or better: 8.8% vs. 0%

VGPR or better: 29.9% vs. 1.0%

First-line MM treatment initiation @ 5yrs: 29.7% vs. 55.9% (HR: 0.46 [0.33–0.62])

Grade ≥3 AEs: 40.4% vs. 30.1%

Hypertension (5.7% vs. 4.6%), infections (16.1% vs. 4.6%), pneumonia (3.6% vs. 0.5%)

Treatment discontinuation due to AEs: 5.7% vs. 0%

Deaths due to AEs: 1.0% vs. 2.0%

Reviewed by Ulas D. Bayraktar, MD on Jun 2, 2025