Researchers of the phase 3 Aquila study presented at the 66th ASH Annual Meeting and showed that daratumumab (D) monotherapy significantly delays progression in patients with high-risk smoldering multiple myeloma (SMM) compared with active monitoring. In the study of 390 patients, those treated with D had notably improved progression-free survival (PFS) (HR = 0.49; p<0.001), with a 60-month PFS rate of 63.1% vs 40.8% in the monitoring group. Median PFS was not reached in the D arm, while it was 41.5 months in the monitoring group. These results were consistent across subgroups, and overall response rates were significantly higher with D (63.4% vs 2.0%).

Additionally, time to first-line treatment for active MM was longer in the D group, with only 33% initiating therapy by data cutoff, compared to 52% in the monitoring group. Median time to treatment was not reached for D, vs 50.2 months for monitoring. A trend toward improved PFS2 and overall survival was also observed with D. Researchers suggest early intervention with D monotherapy may be practice-changing for patients with high-risk SMM, especially in those with specific risk factors such as ≥10% clonal bone marrow plasma cells and other high-risk disease markers.

Reference: Pullen L. Daratumumab Shows Better Outcomes Than Active Monitoring for Smoldering Multiple Myeloma. ASH Clinical News. Published January 2025. Accessed April 14, 2025. https://ashpublications.org/ashclinicalnews/news/8386/Daratumumab-Shows-Better-Outcomes-Than-Active