Multinational phase 3 trial of daratumumab versus active monitoring for high-risk smoldering multiple myeloma

The multinational phase 3 AQUILA trial randomized patients with smoldering multiple myeloma to subcutaneous daratumumab (anti-CD38) or active monitoring. Primary endpoint was progression to active multiple myeloma. With a median follow-up of 65.2 months, the risk of disease progression or death was 51% lower with daratumumab than with active monitoring (HR 0.49; p<0.001). Overall survival rate at 5 years was 93.0% with daratumumab and 86,9% with active monitoring (HR 0.52; 95% CI 0.27-0.98). The most common grade 3 or 4 adverse even was hypertension, which occurred in 5.7% and 4.6% of the patients in the daratumumab group and the active monitoring group, respectively. Adverse events led tot discontinuation of daratumumab in 5.7% of patients in the daratumumab group. No new safety concerns were identified. The authors conclude that among patients with high-risk smoldering multiple myeloma, subcutaneous daratumumab monotherapy was associated with a significantly lower risk of progression to active multiple myeloma or death and higher overall survival than active monitoring.