Daratumumab is a human CD38 IgGκ monoclonal antibody that demonstrated significant activity and a manageable safety profile when used in combination with bortezomib and dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma.
Investigators of the CASTOR trial examined patient subgroups to compare the efficacy of adding daratumumab to bortezomib plus dexamethasone in bortezomib-naive and bortezomib-experienced patient populations. The investigators also evaluated the efficacy of the combination of daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone alone in patients with disease refractory to lenalidomide as their last previous line of therapy.
The median follow-up was 13 months, which is the longest period for this treatment regimen.
The subgroup analysis showed the following outcomes:
Bortezomib-naive patients (N = 172): The median progression-free survival (PFS) was not reached when adding daratumumab to bortezomib plus dexamethasone, and was 7.5 months with bortezomib and dexamethasone alone; the estimated 12-month PFS rates were 74.6% and 32.3%, respectively.
Bortezomib-exposed patients (N = 326): The median PFS was 12.4 months when adding daratumumab to the 2 drugs versus 6.7 months with bortezomib and dexamethasone alone; the estimated 12-month PFS rates were 51.3% and 15.2%, respectively.
Lenalidomide-refractory patients (N = 105): The median PFS was 9.3 months with daratumumab added to the 2 drugs versus 4.4 months with bortezomib and dexamethasone alone.
The objective response rates, including very good partial response or better, improved significantly when adding daratumumab to bortezomib and dexamethasone in all subsets of patients with multiple myeloma.
According to the investigators, these subset analyses confirm that the addition of daratumumab to the combination of bortezomib and dexamethasone significantly improves outcomes for patients with relapsed or refractory multiple myeloma, regardless of whether or not they received previous treatment with bortezomib.
In addition, the benefit of adding daratumumab to bortezomib and dexamethasone versus bortezomib and dexamethasone alone was maintained in patients with disease refractory to lenalidomide as their last previous line of therapy.