- In patients with newly diagnosed multiple myeloma (NDMM) eligible for autologous stem-cell transplantation (ASCT), daratumumab plus standard of care (D-VTd) improved depth of response and progression-free survival (PFS) compared with standard of care (bortezomib/thalidomide/dexamethasone, VTd) alone.
- The combination, administered before and after ASCT, was well tolerated.
Why this matters
- D-VTd is effective in transplant-ineligible NDMM patients.
- This is the first study showing the clinical benefit of D-VTd in transplant-eligible NDMM patients.
- The two-part, phase 3 CASSIOPEIA trial enrolled 1085 transplant-eligible NDMM patients.
- Patients were randomly assigned (1:1) to receive 4 pre-transplant induction and 2 post-transplant consolidation cycles of VTd alone or in combination with daratumumab (D-VTd).
- The primary endpoint was the rate of post-consolidation stringent complete response (sCR) assessed at Day 100 post-ASCT.
- Part 2 of the study (maintenance) is currently ongoing.
- sCR rate was significantly higher in the D-VTd arm (29% vs 20%; OR 1.60 [95%CI 1.21-2.12]; P=0.0010).
- 39% of patients in the D-VTd arm and 26% in the VTd arm achieved a complete response or better, 64% of patients in the D-VTd arm and 44% in the VTd arm achieved minimal residual disease-negativity (10−5, assessed by multiparametric flow cytometry; both P
- With median PFS not reached in either arm, 18-month PFS rates were 93% versus 85% in the D-VTd and VTd arm, respectively (HR 0.47 [95% CI 0·33–0·67]; P
- 46 deaths on study were observed (14 in the D-VTd arm and 32 in the VTd arm; HR 0.43 [95% CI, 0.23-0.80], however overall survival data are immature.
- The most common grade 3 or 4 adverse events were neutropenia (28% in the D-VTd arm vs 15% in the VTd arm), lymphopenia (17% vs 10%), thrombocytopenia (11% vs 7%), and stomatitis (13% vs 16%).