INTRODUCTION: The presence of high-risk chromosomal abnormalities [t(4;14), del(17p), and t(14;16)] has been linked with inferior outcomes in patients with multiple myeloma (MM). A prespecified interim analysis of the Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) + carfilzomib (K) and dexamethasone (d; Isa-Kd) significantly improved progression-free survival (PFS) versus Kd in patients with relapsed MM. This prespecified subgroup analysis of IKEMA examined efficacy and safety in patients with high-risk cytogenetics. METHODS: High-risk cytogenetics was assessed by central laboratory and patients were classified as high risk if abnormalities were present in ≥1 of the following: del(17p): 50% cutoff; t(4;14), and/or t(14;16): 30% cutoff. RESULTS: Of the randomized patients, 23.5% (Isa-Kd) and 25.2% (Kd) had ≥1 high-risk chromosomal abnormality. A PFS benefit was seen in favor of Isa-Kd for patients with standard-risk (HR 0.440; 95% CI 0.266-0.728) and high-risk cytogenetics (HR 0.724; 95% CI 0.361-1.451). Grade ≥3 treatment-emergent adverse events (TEAEs) were more common with Isa-Kd (85.7%) versus Kd (63.3%) in patients with high-risk cytogenetics; however, the incidence of serious TEAEs (64.3% vs. 66.7%) was similar. CONCLUSIONS: Isa-Kd is a new treatment option for the difficult-to-treat subgroup of patients with relapsed MM and high-risk cytogenetics.

1st Department of Medicine Department of Hematology 1st Faculty of Medicine Charles University and General Hospital Prague Czech Republic

Austin and Repatriation Medical Center Heidelberg Victoria Australia

Department of Haematology Lille University Hospital Lille France

Department of Haematology University College Hospital London UK

Department of Hematology and Stem Cell Transplantation National Institute for Hematology and Infectious Diseases South Pest Central Hospital Budapest Hungary

Dipartimento di Medicina Specialistica Diagnostica e Sperimentale Università di Bologna Bologna Italy

Gazi University Ankara Turkey

Hematology Department Institut Català d'Oncologia and Josep Carreras Institute Hospital Germans Trias i Pujol Badalona Spain

Hospital Clinic IDIBAPS Barcelona Spain

Hospital das Clínicas de Faculdade de Medicina da Universidade de São Paulo São Paulo Brazil

IRCCS Azienda Ospedaliero Universitaria di Bologna Istituto di Ematologia Seràgnoli Bologna Italy

Sanofi Cambridge Massachusetts USA

Sanofi R and D Chilly Mazarin France

Sanofi R and D Vitry Sur Seine France

Seoul National University Hospital Seoul South Korea

University of California San Francisco San Francisco California USA

University of Nantes Nantes France

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