B01 | ANALYSIS OF SUSTAINED MINIMAL RESIDUAL DISEASE NEGATIVITY IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA TREATED WITH CARFILZOMIB-LENALIDOMIDE-DEXAMETHASONE WITH OR WITHOUT ISATUXIMAB (PHASE III ISKIA TRIAL)

Background. The phase III IsKia trial evaluated isatuximab-carfilzomib-lenalidomide-dexamethasone (IsaKRd) as pre-ASCT induction and post-ASCT consolidation vs KRd in NDMM patients (pts). Here we report the rates of 1-year sustained (sust)MRD negativity and results from the light consolidation phase. Methods. Transplant-eligible NDMM pts aged <70 years were enrolled. IsaKRd pts received 4 full-dose IsaKRd induction cycles, MEL200-ASCT, 4 full-dose IsaKRd consolidation cycles, and, thereafter, 12 28-day light consolidation cycles [Isa 10 mg/kg IV on days (dd) 1, 15; K 56 mg/m<sup>2</sup> IV dd 1; R 10 mg PO daily dd 1–21; d 20 mg PO dd 1, 15]. Pts in the KRd arm received the same KRd schedule used in the other arm. MRD was assessed by NGS in all pts who achieved ≥VGPR. 1-year sustMRD negativity was defined as 2 sequential MRD-negative evaluations at least 1 year apart. Based on the ITT principle, pts with missing MRD data or who did not achieve VGPR were considered as MRD positive. The data cut-off was 22/7/2024. Results. 151 vs 151 pts were randomly assigned to IsaKRd vs KRd. Pt characteristics were well balanced. The median follow-up was 35 months (IQR 32–38). In the ITT analysis, the MRD negativity rates at the 10<sup>-5</sup> cut-off after full-dose consolidation were 77% vs 67% (OR 1.67; p=0.049) with IsaKRd vs KRd; the rates of 10<sup>-5</sup> 1-year sustMRD negativity after light consolidation were 66% vs 59% (OR 1.36; p=0.21). The MRD negativity rates at the 10<sup>-6</sup> cut-off after full-dose consolidation were 67% vs 48% (OR 2.29; p<0.001) with IsaKRd vs KRd; the rates of 10<sup>-6</sup> 1-year sustMRD negativity after light consolidation were 52% vs 38% (OR 1.82; p=0.012). The 10<sup>-6</sup> 1-year sustMRD negativity advantage with IsaKRd vs KRd was retained in all subgroups. In particular, 62% vs 20% of pts with ≥2 high-risk CA (OR 6.3, 95% CI 1.11–35.66) and 47% vs 35% of pts with R2-ISS III/IV (OR 1.62, 95% CI 0.77–3.41). During light consolidation, the main grade 3–4 hematologic AE was neutropenia (IsaKRd 17% vs KRd 18%); the main grade 3–4 non-hematologic AEs included infections (8% vs 5%), gastrointestinal (4% vs 4%), and vascular AEs (3% vs 1%); discontinuation for toxicity occurred in 3% vs 2%; treatment-related deaths were 2 (1 cerebral ischemia, 1 pulmonary embolism) vs 0. Conclusion. IsaKRd induction-consolidation and prolonged light consolidation significantly increased the rates of 10<sup>-6</sup> sustMRD negativity in NDMM pts (including high-risk pts) without additional safety issues.