KEY TAKEAWAYS
- The PERSEUS phase 3 trial aimed to showcase the further deepening responses & MRD negativity during maintenance of TE subgroup in pts with NDMM.
- D-R maintenance improved MRD negativity; D-VRd showed higher deep and sustained MRD clearance, enhancing PFS.
In this trial transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM) patients (pts) were randomized to receive either subcutaneous daratumumab (DARA SC) in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) or VRd followed by lenalidomide (R) maintenance. During both induction and maintenance phases, D-VRd treatment showed superior progression-free survival (PFS) and increased rates of complete response and minimal residual disease (MRD) negativity.
Deeper responses were observed in pts treated with D-VRd, over time with higher rates of MRD negativity compared to those receiving VRd followed by R maintenance. These findings support the use of D-VRd followed by D-R maintenance as a new standard of care for TE pts with multiple myeloma (MM), highlighting the clinical benefit of incorporating subcutaneous daratumumab in maintenance therapy.
Pieter Sonneveld and the team determined to report here, the further deepening response and MRD negativity in TE pts with NDMM.
TE pts with NDMM were randomized 1:1 to receive D-VRd or VRd. Each underwent up to 6 28-day cycles (4 pre-ASCT induction, 2 post-ASCT consolidation) of VRd (V 1.3 mg/m² SC on Days 1, 4, 8, 11; R 25 mg PO on days 1-21; d 40 mg PO/IV on Days 1-4, 9-12), followed by R maintenance (10 mg PO on Days 1-28 until PD). D-VRd pts also received DARA SC (DARA 1,800 mg + rHuPH20 [2,000 U/mL; Halozyme]) QW in Cycles 1-2, Q2W in Cycles 3-6, Q4W during maintenance until PD. MRD-negativity rate (clonoSEQ®) was the proportion achieving ≥CR and MRD negativity in pts with ITT.
About 709 randomized pts (D-VRd, n = 355; VRd, n = 354), D-VRd demonstrated superior responses compared to VRd. Rates of ≥CR were significantly higher with D-VRd at the end of consolidation (44.5% vs 34.7%) and overall (87.9% vs 70.1%).
MRD-negativity rates were consistently higher with D-VRd at 12, 24, and 36 months after Cycle 1 Day 1, showing significant improvements compared to VRd (all P < 0.0001). Sustained MRD negativity rates for ≥12 months were also markedly higher with D-VRd across thresholds (10–5: 64.8% vs 29.7%; 10–6: 47.3% vs 18.6%; both P < 0.0001), consistently seen in various patient subgroups.
Among MRD-positive pts post-consolidation, a greater proportion achieved MRD negativity during maintenance with D-VRd compared to VRd, particularly at deeper MRD thresholds (10–5: 68.8% vs 52.7%; 10–6: 62.3% vs 31.0%; both P < 0.0001). Sustained MRD negativity for ≥12 months at both 10–5 and 10–6 thresholds was significantly higher with D-VRd (10–5: PFS).
Further analyses will provide additional insights into response rates across study phases and sustained MRD negativity, highlighting the robustness of D-VRd followed by D-R maintenance as a new standard of care in TE pts with NDMM.
The study concluded that maintenance therapy with D-R assisted in achieving more MRD-positive pts and enhancing the MRD negativity vs R alone. Whereas D-VRd induction followed by D-R maintenance showed superior deep and sustained MRD negativity, correlating with improved PFS, advocating the D-VRd followed by D-R maintenance as an emerging standard for TE pts with NDMM.
The trial was sponsored by Stichting European Myeloma Network.
Source: https://library.ehaweb.org/eha/2024/eha2024-congress/422305
Clinical Trials: https://clinicaltrials.gov/study/NCT03710603
Sonneveld P, Moreau P, Dimopoulos P M, et al. (2024). “Daratumumab + bortezomib/lenalidomide/dexamethasone in transplant-eligible patients with newly diagnosed multiple myeloma: analysis of minimal residual disease in the PERSEUS trial.” Presented at EHA 2024. (abstr 422305; S201), https://library.ehaweb.org/eha/2024/eha2024-congress/422305
