The randomized phase 3 study ENDEAVOR demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for carfilzomib and dexamethasone (Kd) vs bortezomib and dexamethasone (Vd) in relapsed or refractory multiple myeloma (MM). We conducted a preplanned subgroup analysis of ENDEAVOR to evaluate Kd vs Vd by cytogenetic risk. Of 785 patients with known cytogenetics, 210 (27%) had high-risk cytogenetics (Kd, n=97 (25%); Vd, n=113 (28%)) and 575 (73%) had standard-risk cytogenetics (Kd, n=284 (75%); Vd, n=291 (72%)). Median PFS in the high-risk group was 8.8 months for Kd vs 6.0 months for Vd (hazard ratio (HR), 0.65; 95% confidence interval (CI), 0.45-0.92; P=0.0075). Median PFS in the standard-risk group was not estimable for Kd vs 10.2 months for Vd (HR, 0.44; 95% CI, 0.33-0.58; P<0.0001). Overall response rates were 72.2% (Kd) vs 58.4% (Vd) in the high-risk group and 79.2% (Kd) vs 66.0% (Vd) in the standard-risk group. In the high-risk group, 15.5% (Kd) vs 4.4% (Vd) achieved a complete response (CR) or better. In the standard-risk group, 13.0% (Kd) vs 7.9% (Vd) achieved ⩾CR. This preplanned subgroup analysis found that Kd was superior to Vd in relapsed or refractory MM, regardless of cytogenetic risk.

Department of Clinical Haematology Institut Català d'Oncologia Institut Josep Carreras Hospital Germans Trias i Pujol Barcelona Spain

Department of Haematology CHRU Lille Hôpital Claude Huriez Lille France

Department of Haematology Hospital Clínic de Barcelona Barcelona Spain

Department of Haematology Oncology Cancer Science Institute of Singapore National University of Singapore Singapore Singapore

Department of Haematology Oncology National University Cancer Institute National University Health System Singapore Singapore

Department of Haematology Royal Prince Alfred Hospital Camperdown New South Wales Australia

Department of Haematology University of Nantes Nantes France

Department of Haematooncology University Hospital Ostrava Faculty of Medicine University of Ostrava Ostrava Czech Republic

Department of Hematooncology University Hospital Olomouc Olomouc Czech Republic

Department of Internal Medicine Heidelberg Medical University Heidelberg Germany

Department of Medicine Wilhelminen Cancer Research Institute Wilhelminenspital Vienna Austria

Department of Oncology University of Torino Torino Italy

Division of Hematology Department of Translational Medicine Amedeo Avogadro University of Eastern Piedmont Novara Italy

Haematooncology Clinic University Multiprofile Hospital for Active Treatment 'Sveti Georgi' and Medical University Plovdiv Bulgaria

Hematological Department 1st Republican Clinical Hospital of Udmurtia Izhevsk Russia

Multiple Myeloma Center Weill Cornell Medical College New York Presbyterian Hospital New York NY USA

Myeloma Clinic Universitatsklinikum Tubingen Tubingen Germany

Myeloma Group University Hospital Brno Brno Czech Republic

Onyx Pharmaceuticals Inc an Amgen subsidiary South San Francisco CA USA

School of Medicine National and Kapodistrian University of Athens Athens Greece

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