Isatuximab-VRd Boosts PET-/MRD- “Double Negativity” and Delays Progression vs VRd in Transplant-Ineligible NDMM

In the phase 3 IMROZ trial (NCT03319667), 406 transplant-ineligible, newly diagnosed myeloma patients with baseline PET/CT (Isa-VRd n=244; VRd n=162) received quadruplet induction (isatuximab (CD38mAb)-bortezomib-lenalidomide-dexamethasone) or standard VRd, then Isa-Rd or Rd maintenance. Among the 62% who were PET-positive at baseline, Isa-VRd nearly doubled the odds of achieving both PET/CT negativity (FDG Deauville ≤3) and bone-marrow MRD-10-5 clearance vs VRd (OR 1.54, p=0.016); in those with plasmacytomas, double-negative ≥CR reached 44% vs 33%. Median PFS in baseline-PET+ patients was not reached with Isa-VRd vs 49.1 mo with VRd (HR 0.58, p value non-significant in this subset), echoing the 60-mo PFS 63% vs 45% seen in the full IMROZ population. Historical SWOG S0777 data place VRd mPFS at ~43 mo, and ~41 mo in a long term follow-up study. This underscores the added depth and durability of response with isatuximab. Safety was not detailed here, but prior reports show manageable hematologic toxicity without excess infections.

https://ascopubs.org/doi/10.1200/JCO.2025.43.16\_suppl.7551