251 patients were randomised to receive daratumumab; 247 were assigned to the control group. After a median follow-up of 7.4 months, the median progression-free survival (PFS) was not reached (NR) in the daratumumab arm, and 7.2 months in the control group (HR 0.39, p<0.001). The 12 month PFS was 60.7% versus 26.9%, favouring the daratumumab arm. Overall response rate was 82.9% in the daratumumab group versus 63.2% in the control group (p<0.001). Similarly, complete response rates favoured the experimental arm (19.2% v 9.0%, p=0.001).
© NEJM 2016
© NEJM 2016
An update of CASTOR with three years of follow-up has been publishedr, and a more recent abstract presentation confirmed ongoing efficacy at 4 years of follow-up.r With a median follow-up of 47 months, PFS remained significantly prolonged in the daratumumab arm compared to the control arm (median 16.7 vs 7.1 months, P <0.00001). 3-year overall survival was similar at 61% and 51% respectively.
A recent sub-analysis explored the effect of cytogenetic risk on outcomes in the CASTOR data.r In this analysis at median of 40 months follow-up, DVd prolonged PFS compared with Vd in both standard (16.6 vs 6.6 months, p<0.0001) and high (12.6 vs 6.2 months, p=0.0106) cytogenetic risk. Higher rates of MRD negativity and sustained MRD negativity were seen in the DVd group regardless of cytogenetic risk.
The use of once-weekly bortezomib in combination with daratumumab and dexamethasone has not been investigated in prospective studies. Small retrospective studies demonstrate efficacy and tolerability, particularly in patients with pre-existing neuropathy.r