A study presented by Meletios Dimopoulos, MD, of the National and Kapodistrian University of Athens, as part of the SOHO 2025 Annual Meeting, showed that daratumumab monotherapy in patients with high-risk smoldering multiple myeloma (SMM) demonstrated “an opportunity to delay or even prevent end-organ damage and progression to MM while maintaining quality of life and improving survival.”
The phase 3 AQUILA study included 390 adults who were randomized 1:1 to active monitoring (n=196) or subcutaneous daratumumab monotherapy (n=194) for 36 months or until disease progression.
After a median follow-up of 65.2 months, daratumumab significantly reduced the risk of progression to MM or death by 51% compared with active monitoring: 60-month rates: 63.1% versus 40.8%; (hazard ratio [HR], 0.49; P<0.0001).
The progression-free survival benefit was observed across prespecified subgroups. The overall response rate was 63.4% with daratumumab versus 2.0% with active monitoring (P<0.0001).
The percentage of patients who went on to initiate first-line MM treatment was 33.2% with daratumumab and 53.6% with active monitoring; median time to initiation was not reached versus 50.2 months, respectively (HR, 0.46).
Daratumumab also improved progression after the next line of therapy, including first-line MM treatment (60-month rates: 85.9% vs 78.0%; HR, 0.58) and overall survival (60-month rates: 93.0% vs 86.9%; HR, 0.52).
More deaths occurred in the active monitoring cohort (26 vs 15). Less than 6% of patients (5.7%) receiving daratumumab discontinued treatment due to adverse events. Grade 3/4 adverse events occurred in 40.4% and 30.1% of the daratumumab and active monitoring cohorts, respectively, with hypertension being the most frequently reported event (5.7% vs 4.6%).
“Quality of life was maintained and similar between arms across multiple measures/domains,” the authors noted.
Reference
Dimopoulos MA, Voorhees P, Schjesvold F, et al. Phase 3 AQUILA study of daratumumab monotherapy versus active monitoring in patients with high-risk smoldering multiple myeloma (SMM). Abstract #MM-691. Presented at the Society of Hematologic Oncology 2025 Annual Meeting; September 3-6, 2025; Houston, Texas.
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