Daratumumab, a CD38 human monoclonal antibody, demonstrated significant clinical activity in combination with bortezomib and dexamethasone versus bortezomib and dexamethasone alone in the primary analysis of CASTOR, a phase 3 study in relapsed and/or refractory multiple myeloma. A post hoc analysis based on treatment history and longer follow up is presented. After 19.4 (range: 0-27.7) months of median follow up, daratumumab plus bortezomib and dexamethasone prolonged progression-free survival (median: 16.7 versus 7.1 months; hazard ratio, 0.31; 95% confidence interval, 0.24-0.39; P<0.0001) and improved the overall response rate (83.8% versus 63.2%; P<0.0001) compared with bortezomib and dexamethasone alone. The progression-free survival benefit of daratumumab plus bortezomib and dexamethasone was most apparent in patients with 1 prior line of therapy (median: not reached versus 7.9 months; hazard ratio, 0.19; 95% con fidence interval, 0.12-0.29; P<0.0001). Daratumumab plus bortezomib and dexamethasone was also superior to bortezomib and dexamethasone alone in subgroups based on prior treatment exposure (bortezomib, thalidomide, or lenalidomide), lenalidomide-refractory status, time since last therapy (≤12, >12, ≤6, or >6 months), or cytogenetic risk. Minimal residual disease-negative rates were >2.5-fold higher with daratumumab across subgroups. The safety profile of daratumumab plus bortezomib and dexamethasone remained consistent with longer follow up. Daratumumab plus bortezomib and dexamethasone demonstrated significant clinical activity across clinically relevant subgroups and provided the greatest benefit to patients treated at first relapse. Trial registration: clinicaltrials.gov identifier: 02136134.

Albert Schweitzer Hospital Department of Internal Medicine Dordrecht the Netherlands

Ankara University Turkey

Clinical Department of Haematology 1 Medical Department Charles University Prague Czech Republic

Department of Haematology and Stem Cell Transplantation St László Hospital 3 Department of Internal Medicine Semmelweis University Budapest Hungary

Department of Hematology Careggi Hospital and University of Florence Italy

Department of Hematology Oncology Chonnam National University Hwasun Hospital Jeollanamdo South Korea

Department of Hematology Sunderbyn Hospital Luleå Sweden

Department of Medicine University of Colorado Aurora CO USA

Division of Hematology Oncology Columbia University New York NY USA

Division of Hematology Oncology Department of Internal Medicine School of Medicine Medical Research Institute Pusan National University Hospital Busan South Korea

Erasmus Medical Center Rotterdam the Netherlands

Fondazione IRCCS Instituto Nazionale dei Tumori University of Milan Italy

Genmab US Inc Princeton NJ USA

Hospital Angeles Lomas Naucalpan de Juárez y alrededores México

Hospital Santa Marcelina São Paulo Brazil

Instituto do Cancer Hospital Mae de Deus Porto Alegre Brazil

Irmandade Da Santa Casa De Misericordia De São Paulo Brazil

Janssen Research and Development Beerse Belgium

Janssen Research and Development High Wycombe UK

Janssen Research and Development LLC Raritan NJ USA

Janssen Research and Development LLC Spring House PA USA

Malignant Haematology and Stem Cell Transplantation Service Alfred Health Monash University Melbourne Australia

Mayo Clinic Florida Jacksonville FL USA

Oregon Health and Science University Portland OR USA

Royal Adelaide Hospital North Terrace Australia

Seoul St Mary's Hospital South Korea

Seràgnoli Institute of Hematology Department of Experimental Diagnostic and Specialty Medicine University of Bologna Italy

St Vincent's Hospital University of Melbourne Australia

Ulsan University Hospital South Korea

Unite de Genomique du Myelome CHU Rangueil Toulouse France

Universitaetsklinikum Tuebingen der Eberhard Karls Universitaet Abteilung fuer Innere Medizin 2 Tübingen Germany

University Hospital of Salamanca IBSAL Spain

Winship Cancer Institute Emory University Atlanta GA USA

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