Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR

Abstract

Daratumumab, a CD38 human monoclonal antibody, demonstrated significant clinical activity in combination with bortezomib and dexamethasone versus bortezomib and dexamethasone alone in the primary analysis of CASTOR, a phase 3 study in relapsed and/or refractory multiple myeloma. A post hoc analysis based on treatment history and longer follow up is presented. After 19.4 (range: 0–27.7) months of median follow up, daratumumab plus bortezomib and dexamethasone prolonged progression-free survival (median: 16.7 versus 7.1 months; hazard ratio, 0.31; 95% confidence interval, 0.24-0.39; P<0.0001) and improved the overall response rate (83.8% versus 63.2%; P<0.0001) compared with bortezomib and dexamethasone alone. The progression-free survival benefit of daratumumab plus bortezomib and dexamethasone was most apparent in patients with 1 prior line of therapy (median: not reached versus 7.9 months; hazard ratio, 0.19; 95% confidence interval, 0.12-0.29; P<0.0001). Daratumumab plus bortezomib and dexamethasone was also superior to bortezomib and dexamethasone alone in subgroups based on prior treatment exposure (bortezomib, thalidomide, or lenalidomide), lenalidomide-refractory status, time since last therapy (≤12, >12, ≤6, or >6 months), or cytogenetic risk. Minimal residual disease–negative rates were >2.5-fold higher with daratumumab across subgroups. The safety profile of daratumumab plus bortezomib and dexamethasone remained consistent with longer follow up. Daratumumab plus bortezomib and dexamethasone demonstrated significant clinical activity across clinically relevant subgroups and provided the greatest benefit to patients treated at first relapse. Trial registration: clinicaltrials.gov identifier: 02136134.

Bortezomib, cyclophosphamide, dexamethasone versus lenalidomide, cyclophosphamide, dexamethasone in multiple myeloma patients at first relapse

“…It seems reasonable to compare the outcome of VCD and RCD with the corresponding doublets bortezomib plus dexamethasone (VD) or lenalidomide plus dexamethasone (RD). The median PFS of 16·3 months obtained with VCD in our study compares favourably with the Castor trial comparing daratumumab plus bortezomib plus dexamethasone versus bortezomib plus dexamethasone, where the median PFS in the bortezomib plus dexamethasone in patients at first relapse was 7·9 months (Spencer et al , ).…”

Daratumumab-based regimens are highly effective and well tolerated in relapsed or refractory multiple myeloma regardless of patient age: subgroup analysis of the phase 3 CASTOR and POLLUX studies

“…PFS was significantly prolonged with D-Vd versus Vd in the ITT population (median: 16.7 vs 7.1 months; HR, 0.31; 95% CI, 0.24-0.39; P<0.0001; Figure 2C), with 18-month PFS rates of 48.0% versus 7.9%, respectively. 21 Similarly, PFS was significantly prolonged with D-Vd compared with Vd in patients aged ≥ 75 years (median: 17.9 vs 8.1 months; HR, 0.26; 95% CI, 0.10-0.65; P=0.0022; Figure 2C), with 18-month PFS rates of 45.8% versus 0%, respectively. PFS was also significantly prolonged for D-Vd versus Vd in patients aged 65 to 74 years (median: 18.9 vs 6.1 months; HR, 0.25; 95% CI, 0.16-0.40; P<0.0001; Figure 2D).…”

Daratumumab plus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma

“…18 Phase 3 clinical trials have demonstrated that daratumumab-based combinations significantly reduce the risk of progression or death by $50% and induce rapid, deep, and durable responses in RRMM and NDMM, including the absence of minimal residual disease (MRD). [19][20][21] Analyses from the phase 3 CASTOR trial of daratumumab plus bortezomib and dexamethasone (D-Vd) in a subgroup of patients who were lenalidomide refractory at last prior line of therapy 21 and data from the daratumumab plus pomalidomide and dexamethasone arm of the phase 1b MMY1001 trial (89% lenalidomide refractory) 6 suggest that the addition of daratumumab to standard-of-care regimens is effective in lenalidomide-refractory RRMM. In clinical studies, the median duration of the first daratumumab IV infusion was 7.0 hours, because the first infusion requires a larger infusion volume (1,000 mL) and a slower initial infusion rate (50 mL/h) compared with the second infusion (500 mL at 50 mL/h, median duration 4.3 hours) and subsequent infusions (500 mL at 100 mL/h, median duration 3.4 hours).…”