Isatuximab, carfilzomib, lenalidomide and dexamethasone in newly diagnosed multiple myeloma: a randomized phase 3 trial
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Induction and consolidation with a quadruplet therapy of a CD38-targeting monoclonal antibody, a proteasome inhibitor, an immunomodulatory drug and dexamethasone are a standard-of-care treatment in transplant-eligible (TE) patients with newly diagnosed multiple myeloma (NDMM) with the optimal drugs to be used still under debate. The ongoing, phase 3 EMN24 IsKia trial randomized 302 TE patients with NDMM aged ≤70 years 1:1 to isatuximab–carfilzomib–lenalidomide–dexamethasone (Isa-KRd) versus KRd pretransplant induction and post-transplant consolidation. The primary endpoint was the rate of measurable residual disease (MRD) negativity (sensitivity of 10 −5 or better) by next-generation sequencing (NGS) after consolidation. Key secondary endpoints were the rates of NGS-MRD negativity after induction and progression-free survival (PFS). MRD negativity rates at higher sensitivity (10 −6 or better) were exploratory. Post-consolidation MRD negativity was significantly higher with Isa-KRd versus KRd at the 10 −5 (77% versus 67%; odds ratio (OR) 1.67, P = 0.049) and 10 −6 (68% versus 48%; OR 2.36, P = 0.0004) sensitivities. Deep MRD responses were rapid (post-induction Isa-KRd versus KRd: 10 −5 46% versus 27%, OR 2.32, P = 0.0007; 10 −6 28% versus 14%, OR 2.44, P = 0.0029) and durable (1-year sustained 10 −6 MRD negativity 52% versus 38%, OR 1.82, P = 0.012). At current follow-up, PFS data were immature. Grade 3–4 non-hematologic adverse events (AEs), treatment discontinuations and deaths due to AEs were similar in the two arms. Isa-KRd significantly improved NGS-MRD negativity in TE patients with NDMM, with a manageable safety profile. ClinicalTrials.gov registration: NCT04483739 .
Source: Nature Medicine
Authors: Francesca Gay, Wilfried Roeloffzen, Meletios A. Dimopoulos, Laura Rosiñol, Marjolein van der Klift, Roberto Mina, Albert Oriol, Eirini Katodritou, Ka Lung Wu, Paula Rodríguez Otero, Roman Hájek, Elisabetta Antonioli, Mark van Duin, Mattia D’Agostino, Joaquín Martínez-López, Elena M. van Leeuwen-Segarceanu, Elena Zamagni, Niels W. C. J. van de Donk, Katja C. Weisel, Luděk Pour, Jakub Radocha, Angelo Belotti, Fredrik Schjesvold, Joan Bladé, Hermann Einsele, Pieter Sonneveld, Mario Boccadoro, Annemiek Broijl
Institutions: Azienda Ospedaliera Citta' della Salute e della Scienza di Torino, University of Turin, University Medical Center Groningen, Korea University, National and Kapodistrian University of Athens, 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, Erasmus MC Cancer Institute, Universidad Complutense de Madrid, Hospital Universitario 12 De Octubre, St. Antonius Ziekenhuis, Istituto di Ematologia di Bologna, University of Bologna, Amsterdam University Medical Centers, Cancer Center Amsterdam, Vrije Universiteit Amsterdam, University Medical Center Hamburg-Eppendorf, University Hospital Brno, Charles University, University Hospital Hradec Králové, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Oslo University Hospital, University of Oslo, University of Würzburg, Universitätsklinikum Würzburg
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
OpenAlex ID: W7150793289