Positron emission tomography with computed tomography (PET/CT) and minimal residual disease (MRD) for efficacy assessment in transplant-ineligible newly diagnosed myeloma (Ti NDMM) patients (pts): IMROZ analysis.

7551 Background: MRD is a measure of response in the bone marrow (BM) but is limited by patchy infiltration of BM plasma cells and lack of plasmacytoma assessment. Imaging-based MRD assessment, which is non-invasive, such as PET/CT, may overcome these limitations, and distinguish metabolically active MM from non-active. Isatuximab (Isa) is an anti-CD38 monoclonal antibody 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 (NCT03319667), investigating PET/CT negativity (−) with MRD− in front line efficacy assessment. Methods: In IMROZ, pts were randomized 3:2 to receive Isa-VRd or VRd as initiation, then Isa-Rd or Rd as maintenance. BM MRD was assessed by next generation sequencing at 10 -5 sensitivity 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). 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. PET/CT positivity (+) was defined as FDG 5PS Score ≥4, and PET/CT− as FDG 5PS ≤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. Among PET+ pts at BL, the double negativity rate (PET/CT FDG 5PS score ≤3 + 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 5PS ≤3 and MRD−, and PET/CT 5PS ≤3 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, including pts with plasmacytomas. This translated to a better PFS in pts treated with Isa-VRd. Clinical trial information: NCT03319667 . Isa-VRd (n=77) VRd (n=52) PET/CT 5PS score ≤3 and MRD−, % 45.5 34.6 OR (95% CI), p 1.57 (0.76-3.26), 0.1107 PET/CT 5PS score ≤3 and MRD− + ≥CR, % 44.2 32.7 OR (95% CI), p 1.63 (0.78-3.39), 0.0966