DP111 | POSITRON EMISSION TOMOGRAPHY WITH COMPUTED TOMOGRAPHY AND MINIMAL RESIDUAL DISEASE FOR EFFICACY ASSESSMENT IN TRANSPLANT-INELIGIBLE NEWLY DIAGNOSED MYELOMA PATIENTS: IMROZ ANALYSIS

Introduction: MRD is a measure of response in the bone marrow. Imaging-based response assessment, such as PET/CT may distinguish metabolically active MM from non-active. Isatuximab (Isa) is approved in combination with bortezomib, lenalidomide and dexamethasone (VRd) in Ti NDMM pts based on the Phase 3 IMROZ study. Here, we present an analysis of IMROZ, investigating PET/CT negativity (−) with MRD− in front line efficacy assessment. Methods: Pts were randomized 3:2 to receive Isa-VRd or VRd as initiation, then Isa-Rd or Rd as maintenance. MRD was assessed at baseline (BL), then in case of complete response (CR) or very good partial response at end of initiation, and every 6 months for 2 years, then once a year until disease progression (PD) by next generation sequencing at 10-5 sensitivity threshold. PET/CT scans were assessed by central review and performed at BL, then yearly until PD; if positive for soft tissue plasmacytoma, repeated at time of CR and/or end of induction, then following time points for MRD assessment. BL PET/CT positivity (+) was defined as FDG 5PS Score ≥4, and complete metabolic response (CMR) was a Deauville score of ≤3. Results: Across the global and China populations, 244 Isa-VRd and 162 VRd pts had PET/CT at BL, of which 153 (62.7%) and 101 (62.3%) were PET/CT+, respectively. Of these, 121 (41.6%) and 83 (43.0%) had a post-BL PET/CT assessment. 155 pts presented with plasmacytoma at BL (95 Isa-VRd, 60 VRd), with comparable BL characteristics to the global population. The double negativity rate (PET/CT FDG 5PS score ≤3 and MRD−) was significantly higher in Isa-VRd pts than VRd (odds ratio [OR] 1.54; 95% CI 1.04-2.29; p=0.0155), and similarly for double negativity + ≥CR (OR 1.60; 95% CI 1.07-2.38; p=0.0108). As shown in Table, more Isa-VRd than VRd pts with plasmacytoma reached PET/CT CMR and MRD−, and PET/CT CMR with MRD− + ≥CR. Progression-free survival (PFS) in pts PET/CT+ at BL was in favor of the Isa-VRd arm (median PFS [mPFS] not reached [NR; 95% CI 59.4-NR]) vs VRd (mPFS 49.1 [95% CI 39.1 -NR]) (hazard ratio [HR] 0.58; 95% CI 0.39-0.88; p=0.6303), and HR was comparable to the intent to treat population. PFS in pts with plasmacytoma at BL was similar to the global population (HR 0.685; 95% CI 0.40-1.18; p=0.5332). Conclusions: This analysis of IMROZ shows the prognostic value of BL PET/CT findings. More Isa-VRd pts reached double negativity than VRd, regardless of whether pts had plasmacytomas.