AQUILA
Trial question
What is the role of daratumumab monotherapy in patients with high-risk smoldering myeloma?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
52.0% female
48.0% male
N = 390
390 patients (202 female, 188 male).
Inclusion criteria: adult patients with high-risk smoldering myeloma.
Key exclusion criteria: multiple myeloma requiring treatment; primary systemic amyloid light-chain amyloidosis; prior exposure to daratumumab; ongoing treatment with other monoclonal antibodies; receipt of treatment for malignancy in the past 3 years; medical or psychiatric condition or disease.
Interventions
N=194 daratumumab (subcutaneous dose of 1,800 mg on a weekly basis in cycles 1-2, every 2 weeks in cycles 3-6, and every 4 weeks thereafter in 28-day cycles continued for up to 39 cycles or for 36 months).
N=196 active monitoring (no disease-specific treatment for 36 months or until confirmation of disease progression).
Primary outcome
Progression-free survival
65.5%
49.5%
65.5 %
49.1 %
32.8 %
16.4 %
0.0 %
Daratumumab
Active
monitoring
Significant
increase ▲
NNT = 6
Significant increase in progression-free survival (65.5% vs. 49.5%; HR 2.04, 95% CI 1.49 to 2.78).
Secondary outcomes
Significant increase in overall survival (92.3% vs. 86.7%; HR 1.92, 95% CI 1.02 to 3.7).
Significant decrease in initiation of first-line treatment (33.2% vs. 53.6%; HR 0.46, 95% CI 0.33 to 0.62).
Safety outcomes
No significant difference in hypertension.
Conclusion
In adult patients with high-risk smoldering myeloma, daratumumab was superior to active monitoring with respect to a progression-free survival.
Reference
Meletios A Dimopoulos, Peter M Voorhees, Fredrik Schjesvold et al. Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma. N Engl J Med. 2024 Dec 9. Online ahead of print.
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