EC approves SC daratumumab for the treatment of HR smoldering MM

On July 23, 2025, the European Commission approved subcutaneous daratumumab monotherapy for the treatment of patients with high-risk (HR) smoldering multiple myeloma (MM).

This approval represents the first authorized treatment for patients with HR smoldering MM, and was based on data from the phase III AQUILA study (NCT03301220). The Multiple Myeloma Hub has previously reported the safety and efficacy results from AQUILA.

AQUILA pivotal data

• Treatment with daratumumab resulted in a significantly improved 60-month progression-free survival rate at 63.1% vs 40.8% in patients undergoing active monitoring (HR, 0.49; 95% CI, 0.36–0.67; p < 0.001).
• There was also a numerically higher 5-year overall survival rate observed with daratumumab vs active monitoring at 93.0% and 86.9%, respectively.
• The median time to treatment initiation for active MM was not reached among patients who received daratumumab and was 50.2 months for patients undergoing active monitoring (HR, 0.46; 95% CI, 0.33–0.62; p < 0.0001).
• The safety profile for daratumumab was consistent with that observed in previous studies.
• The incidence of Grade 3/4 treatment-emergent adverse events (TEAEs) was higher with daratumumab treatment at 40.4% vs 30.1% with active monitoring.
• The most common TEAE observed in either cohort was hypertension.
• TEAEs leading to discontinuation of daratumumab occurred in 5.7% of patients, with 1% experiencing a fatal TEAE.