Bortezomib, thalidomide, and dexamethasone (VTd) plus autologous stem-cell transplantation (ASCT) is standard treatment in Europe for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM).
It was evaluated whether the addition of daratumumab to VTd before and after ASCT would improve stringent complete response (sCR) rate in patients with NDMM.
In this two-part, randomised, phase 3 CASSIOPEIA trial, the researchers recruited transplant-eligible patients with NDMM at 111 European sites.
The results of this study were presented at the 2019 European Hematology Association (EHA) Annual Meeting.
Patients were randomly assigned (1:1) to receive four pre-transplant induction and two post-transplant consolidation cycles of VTd alone (VTd group) or in combination with daratumumab (D-VTd group).
The primary endpoint of part 1 was sCR assessed after consolidation.
Part 2, the maintenance, is ongoing.
Between Sept 22, 2015, and Aug 1, 2017, 1085 patients were enrolled and were randomly assigned to the D-VTd group (n=543) or the VTd group (n=542).
After consolidation, 157 (29%) of 543 patients in the D-VTd group and 110 (20%) of 542 patients in the VTd group in the intention-to-treat population had achieved a sCR (odds ratio 1·60, 95% CI 1·21–2·12, p=0·0010). 211 (39%) patients in the D-VTd group versus 141 (26%) in the VTd group achieved a complete response or better, and 346 (64%) of 543 versus 236 (44%) of 542 achieved minimal residual disease-negativity (10 −5, assessed by multiparametric flow cytometry; both p<0·0001).
Median progression-free survival from first randomisation was not reached in either group (hazard ratio 0·47, 95% CI 0·33–0·67, p<0·0001). 46 deaths on study were observed (14 vs 32, 0·43, 95% CI 0·23–0·80).
The most common grade 3 or 4 adverse events were neutropenia (28% vs 15%), lymphopenia (17% vs 10%), and stomatitis (13% vs 16%).
D-VTd before and after ASCT improved depth of response and progression-free survival with acceptable safety.
CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with NDMM.