Background
Randomized phase 3 trial of 498 patients with relapsed/refractory multiple myeloma who had received ≥1 prior line, comparing daratumumab plus bortezomib and dexamethasone (DVd) vs bortezomib and dexamethasone (Vd).
Interventions and follow up
Arm A (DVd): Daratumumab 16 mg/kg IV (D1,8,15 C1-3, then Q3W C4-8, then Q4W) + bortezomib + dexamethasone, 21-day cycles
Arm B (Vd): Bortezomib 1.3 mg/m2 D1,4,8,11 (C1-8) + dexamethasone 20 mg D1,2,4,5,8,9,11,12
Primary endpoint: PFS
Median follow-up: 7.4 months
Arm B (Vd): Bortezomib 1.3 mg/m2 D1,4,8,11 (C1-8) + dexamethasone 20 mg D1,2,4,5,8,9,11,12
Primary endpoint: PFS
Median follow-up: 7.4 months
Results
Median PFS: not reached (DVd) vs 7.2 months (Vd); HR 0.39, 95% CI 0.28-0.53, P<.001
12-month PFS: 60.7% vs 26.9%
12-month PFS: 60.7% vs 26.9%
Adverse events
Hematologic (grade 3-4): Thrombocytopenia 45.3% (DVd) vs 32.9% (Vd); anemia 14.4% vs 16%; neutropenia 12.8% vs 4.2%
Infusion reactions: Daratumumab-associated reactions in 45.3% (mostly grade 1-2; 8.6% grade 3), 98.2% occurring with the first infusion
Infusion reactions: Daratumumab-associated reactions in 45.3% (mostly grade 1-2; 8.6% grade 3), 98.2% occurring with the first infusion
Conclusions
In relapsed/refractory multiple myeloma, daratumumab added to bortezomib and dexamethasone significantly prolonged PFS compared with Vd alone.
Key Limitations
Short median follow-up (7.4 months) at primary analysis with immature OS. Fixed-duration bortezomib (8 cycles) in both arms differs from continuous-therapy comparators. Daratumumab interference with serologic response assessment and blood typing.
Clinical Context
CASTOR supported FDA and EMA approval of daratumumab plus bortezomib and dexamethasone for relapsed/refractory multiple myeloma after ≥1 prior therapy. DVd is a recognized triplet option at relapse, particularly for lenalidomide-exposed patients, per ASCO and ESMO guidance.