In this subgroup analysis of the randomized, Phase 3 IKEMA study (NCT03275285), we evaluated efficacy and safety of the anti-CD38 monoclonal antibody isatuximab (Isa) in combination with carfilzomib-dexamethasone (Isa-Kd) versus Kd in older (≥70 years of age, n = 86) and younger (<70 years, n = 216) patients with relapsed multiple myeloma (MM). Patients received Isa 10 mg/kg intravenously weekly for 4 weeks, then every 2 weeks in the Isa-Kd arm, and approved schedule of carfilzomib (twice weekly) and dexamethasone in both study arms. Primary endpoint was progression-free survival (PFS); key secondary efficacy endpoints included rates of overall response (ORR), very good partial response or better (≥VGPR), minimal residual disease negativity (MRD-), and complete response (CR). Addition of Isa to Kd resulted in improved PFS in elderly patients (hazard ratio, 0.36 [95% CI, 0.18-0.75]) consistent with the significant PFS improvement observed in the overall IKEMA population. Treatment with Isa-Kd improved depth of response versus Kd, with higher rates of ≥VGPR (73.1% vs. 55.9%), MRD- (23.1% vs. 11.8%), and CR (38.5% vs. 23.5%). Although the incidence of grade ≥3 treatment-emergent adverse events (TEAEs) was higher in Isa-Kd, the incidence of serious TEAEs was similar between arms. Fewer elderly patients definitively discontinued treatment due to TEAEs in Isa-Kd than Kd: 11.8% versus 23.5%. In conclusion, Isa-Kd provides a consistent benefit versus Kd in elderly patients, with a manageable safety profile, and represents a new treatment option for patients with relapsed MM, independent of age.

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

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

Gazi University Ankara Turkey

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

Hospital Clinic IDIBAPS Barcelona Spain

Hospital das Clínicas de São Paulo São Paolo Brazil

IRCCS Azienda Ospedaliero Universitaria di Bologna Seràgnoli Institute of Hematology Bologna University School of Medicine Bologna Italy

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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