D-VRd (daratumumab anti-CD38) drives 65% sustained MRD− and >95% 4-year PFS in TE NDMM

Subcutaneous daratumumab (anti-CD38 mAb) plus bortezomib/lenalidomide/dexamethasone (D-VRd) with daratumumab+lenalidomide (D-R) maintenance was evaluated vs VRd with lenalidomide maintenance in the Phase 3 PERSEUS trial in transplant-eligible newly diagnosed multiple myeloma (NCT03710603; n=709). At 47.5 months’ median follow-up, ≥12-month sustained MRD negativity (10^-5; ITT) was 64.8% with D-VRd/D-R vs 29.7% with VRd/R; ≥24-month sustained MRD negativity was 55.8% vs 22.6%, respectively, and sustained MRD negativity (≥12 months) tracked with >95% 48-month PFS in the D-VRd arm. As a clinical “early relapse” signal, functionally high-risk progression ≤18 months was lower with D-VRd vs VRd (3.1% vs 6.8%)—consistent with the broader PERSEUS PFS advantage at ~4 years (48-month PFS 84.3% vs 67.7%; HR 0.42; P<0.001), which now anchors D-VRd as a key US standard for TE NDMM rather than VRd triplet alone.