BY: Kerri Fitzgerald
Researchers observed delayed progression to multiple myeloma (MM) in patients with smoldering MM (SMM) who were treated with single-agent daratumumab.
Ola Landgren, MD, PhD, of the University of Miami Miller School of Medicine, and colleagues published the final analysis of the phase 2 CENTAURUS study in Blood.
The study included 123 patients with intermediate or high-risk SMM who received intravenous daratumumab 16 mg/kg at three dose schedules (n=41 in each group):
- Long-intense (every week in cycle one, every other week in cycles two to three, every four weeks in cycles four to seven, and every eight weeks in cycles eight to 20)
- Intermediate (every week in cycle one and every eight weeks thereafter for cycles two to 20)
- Short-intense (every week for cycle one)
The long-intense dosing schedule appeared the be the most optimal, aligning with the approved daratumumab dosing schedule for MM.
After a combined median follow-up of just over seven years (85.2 months), complete response rates were:
- 9% in the long-intense group
- 8% in the intermediate group
- 0% in the short-intense group
Overall response rates were:
- 5% in the long-intense group
- 7% in the intermediate group
- 5% in the short-intense group
The rates of progressive disease or death were 0.096, 0.102, and 0.109, respectively (P<.0001 for all).
Median progression-free survival was not reached in the long-intense cohort; it was 84.4 months in the intermediate cohort and 74.1 months in the short-intense group. Median overall survival was not reached in any dosing cohort.
Some patients (n=36) in the long-intense or intermediate arms opted to continue daratumumab beyond the protocol-driven 20 cycles. The median treatment duration was 44.0, 35.2, and 1.6 months in the long-intense, intermediate, and short-intense arms, respectively.
The researchers reported no new safety signals.
Phase 3 trials should be conducted to confirm the use of single-agent daratumumab in SMM.
Reference
Landgren O, Chari A, Cohen YC, et al. Efficacy and safety of daratumumab in intermediate/high-risk smoldering multiple myeloma: final analysis of CENTAURUS. Blood. 2025;145(15):1658-1669. doi:10.1182/blood.2024025897
