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)
Year: 2025
Type: article
Abstract: 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/m2 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 10-5 cut-off after full-dose consolidation were 77% vs 67% (OR 1.67; p=0.049) with IsaKRd vs KRd; the rates of 10-5 1-year sustMRD negativity after light consolidation were 66% vs 59% (OR 1.36; p=0.21). The MRD negativity rates at the 10-6 cut-off after full-dose consolidation were 67% vs 48% (OR 2.29; p<0.001) with IsaKRd vs KRd; the rates of 10-6 1-year sustMRD negativity after light consolidation were 52% vs 38% (OR 1.82; p=0.012). The 10-6 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 10-6 sustMRD negativity in NDMM pts (including high-risk pts) without additional safety issues.
Source: Haematologica
Authors: F. Gay, W. Roeloffzen, M.A. Dimopoulos, L. Rosiñol, M. Van Der Klift, A. Oriol, E. Katodritou, K. L. Wu, P. Rodríguez Otero, R. Hájek, I. Attucci, E. Zamagni, M. Van Duin, M. D'agostino, A. Belotti, S. Mangiacavalli, M. Grasso, G. Margiotta Casaluci, M. Offidani, G.M. De Sabbata, F. Fioritoni, P. Tosi, P. Musto, F. Schjesvold, J. Bladé, H. Einsele, P. Sonneveld, M. Boccadoro, A. Broijl
Institutions: University of Turin, University Medical Center Groningen, Korea University, National and Kapodistrian University of Athens, Korea University, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Amphia Ziekenhuis, Josep Carreras Leukaemia Research Institute, Institut Català d'Oncologia, Theageneio General Hospital, Clinica Universidad de Navarra, University of Ostrava, University Hospital Ostrava, Azienda Ospedaliero-Universitaria Careggi, Istituto di Ematologia di Bologna, University of Bologna, Erasmus MC Cancer Institute, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Policlinico San Matteo Fondazione, Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo, Azienda Ospedaliero Universitaria Maggiore della Carita, Marche Polytechnic University, Azienda sanitaria universitaria Giuliano Isontina, Ospedale Infermi di Rimini, University of Bari Aldo Moro, Oslo University Hospital, University of Oslo, Universitätsklinikum Würzburg
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,157
OpenAlex ID: W4415352556