EHA 2017. LB2236. Daratumumab, Bortezomib and Dexamethasone (DVd) vs Bortezomib and Dexamethasone (Vd) in Relapsed or Refractory Multiple Myeloma (RRMM): Efficacy and Safety Update (CASTOR)
Antonio Palumbo et al.
Results: PFS Data
Conclusions: Daratumumab significantly improved PFS, TTP, and ORR in combination with Vd versus Vd alone. DVd doubled rates of both VGPR or better and stringent CR/CR versus Vd alone. Safety of DVd is consistent with the known safety profile of daratumumab and Vd. The addition of daratumumab to Vd should be considered a new standard of care for patients with RRMM currently receiving Vd alone.
ASCO 2017. 8006. Efficacy of Daratumumab in Combination with Lenalidomide Plus Dexamethasone (DRd) or Bortezomib Plus Dexamethasone (DVd) in Relapsed or Refractory Multiple Myeloma (RRMM) Based on Cytogenetic Risk Status
Katja Weisel et al.
Results: Samples from 311/569 pts in POLLUX and 353/498 pts in CASTOR were assessed via NGS. In POLLUX, the median duration of follow-up was 17.3 months. Significantly longer median PFS and numerically higher ORR were observed with DRd vs Rd among high-risk patients, and significant improvements in these outcomes were observed in std-risk patients. In CASTOR, the median duration of follow-up was 13.0 months. Significantly longer median PFS and higher ORR were observed with DVd vs Vd among both high- and std-risk pts. Concordance rates for t(4;14), t(14;16), and del17p were high (88%-98%) between NGS and FISH. Updated data, including subgroup analyses, will be presented.
Conclusions: In RRMM pts, the addition of D to standard-of-care regimens improved outcomes regardless of cytogenetic risk status. Targeting CD38 by combining D with Rd or Vd appears to improve the poor outcomes associated with high-risk cytogenetic status. Clinical trial information: NCT02136134 and NCT02076009
CARE Faculty Perspective: These data (LB2236 & 8006) reinforce the benefit of daratumumab and dexamethasone in combination with bortezomib or lenalidomide for patients who have received at least one prior therapy. These regimens were approved by Health Canada in April 2017.
The combination of daratumumab with pomalidomide and dexamethasone received FDA approval in June 2017, for patients who have received at least two prior therapies including lenalidomide or a proteasome inhibitor. This was based on clinical trial results from the phase 1 EQUULEUSstudy, which showed an overall response rate of 59.2 percent with the daratumumab triplet. We wait on approval in Canada.
This designation reinforces the versatility of daratumumab with a range of treatment regimens and provides an urgently needed option for this patient sub-group. Daratumumab is also being investigated as a front-line therapy for patients with multiple myeloma in Phase 3 clinical trials.