This randomized, phase III, open-label, multicenter study compared carfilzomib monotherapy against low-dose corticosteroids and optional cyclophosphamide in relapsed and refractory multiple myeloma (RRMM). Relapsed and refractory multiple myeloma patients were randomized (1:1) to receive carfilzomib (10-min intravenous infusion; 20 mg/m2 on days 1 and 2 of cycle 1; 27 mg/m2 thereafter) or a control regimen of low-dose corticosteroids (84 mg of dexamethasone or equivalent corticosteroid) with optional cyclophosphamide (1400 mg) for 28-day cycles. The primary endpoint was overall survival (OS). Three-hundred and fifteen patients were randomized to carfilzomib (n=157) or control (n=158). Both groups had a median of five prior regimens. In the control group, 95% of patients received cyclophosphamide. Median OS was 10.2 (95% confidence interval (CI) 8.4-14.4) vs 10.0 months (95% CI 7.7-12.0) with carfilzomib vs control (hazard ratio=0.975; 95% CI 0.760-1.249; P=0.4172). Progression-free survival was similar between groups; overall response rate was higher with carfilzomib (19.1 vs 11.4%). The most common grade ⩾3 adverse events were anemia (25.5 vs 30.7%), thrombocytopenia (24.2 vs 22.2%) and neutropenia (7.6 vs 12.4%) with carfilzomib vs control. Median OS for single-agent carfilzomib was similar to that for an active doublet control regimen in heavily pretreated RRMM patients.

Amedeo Avogadro University of Eastern Piedmont Novara Italy

AZ Sint Jan Brugge Belgium

Center for Oncology Hematology with Outpatient Department and Palliative Care Wilhelminenspital Vienna Austria

Chaim Sheba Medical Center Tel Hashomer Israel

Charles University Teaching Hospital Hradec Králové Czech Republic

Clinica di Ematologia Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona Ancona Italy

Clínica Universidad de Navarra CIMA IDISNA Navarra Spain

Hadassah Medical Center Jerusalem Israel

Hopital Huriez CHRU Lille France

Hospital Clínic de Barcelona Barcelona Spain

Hospital Elisabethinen Linz Linz Austria

Institut Català d'Oncologia Hospital Germans Trias i Pujol Barcelona Spain

Medical University of Vienna Vienna Austria

Meir Medical Center Kfar Saba Israel

National and Kapodistrian University of Athens Athens Greece

Nicolaus Copernicus Hospital Toruń Poland

Onyx Pharmaceuticals Inc an Amgen subsidiary South San Francisco CA USA

Petz Aladár Megyei Oktató Kórház Vasvári Pál Hungary

Sapienza University of Rome Rome Italy

Southampton General Hospital Hampshire UK

St István and St László Hospital of Budapest Budapest Hungary

University College London Cancer Institute London UK

University Hospital La Fe and Universidad Católica de València 'San Vicente Mártir' València Spain

University Hospital Olomouc and Medical Faculty of Palacky University Olomouc Olomouc Czech Republic

University Hospital Ostrava and Faculty of Medicine University of Ostrava Ostrava Czech Republic

University Medicine Mainz Mainz Germany

University of Pécs Pécs Hungary

University of Torino Torino Italy

Wilhelminen Cancer Research Institute Vienna Austria

Zamojski Szpital Niepubliczny Zamosc Poland

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Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting

Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials

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NCT01302392