In the primary analysis of the phase III COLUMBA study, daratumumab by subcutaneous administration (DARA SC) demonstrated non-inferiority to intravenous administration (DARA IV) for relapsed or refractory multiple myeloma (RRMM). Here, we report the final analysis of efficacy and safety from COLUMBA after a median of 29.3 months follow-up (additional 21.8 months after the primary analysis). In total, 522 patients were randomized (DARA SC, n=263; DARA IV, n=259). With longer follow-up, DARA SC and DARA IV continued to show consistent efficacy and maximum trough daratumumab concentration as compared with the primary analysis. The overall response rate was 43.7% for DARA SC and 39.8% for DARA IV. The maximum mean (standard deviation [SD]) trough concentration (cycle 3, day 1 pre-dose) of serum DARA was 581 (SD, 315) μg/mL for DARA SC and 496 (SD, 231) μg/mL for DARA IV. Median progression-free survival was 5.6 months for DARA SC and 6.1 months for DARA IV; median overall survival was 28.2 months and 25.6 months, respectively. Grade 3/4 treatment-emergent adverse events occurred in 50.8% of patients in the DARA SC group and 52.7% in the DARA IV group; the most common (≥10%) were thrombocytopenia (DARA SC, 14.2%; DARA IV, 13.6%), anemia (13.8%; 15.1%), and neutropenia (13.1%; 7.8%). The safety profile remained consistent with the primary analysis after longer follow-up. In summary, DARA SC and DARA IV continue to demonstrate similar efficacy and safety, with a low rate of infusion-related reactions (12.7% vs. 34.5%, respectively) and shorter administration time (3-5 minutes vs. 3-7 hours) supporting DARA SC as a preferable therapeutic choice. (Clinicaltrials gov. Identifier: NCT03277105.

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

Arnie Charbonneau Cancer Research Institute University of Calgary Calgary AB

Center of Oncology of the Lublin Region St Jana z Dukli Lublin

Clinica Medica São Germano São Paulo

Dalhousie University and Queen Elizabeth 2 Health Science Centre Halifax NS

Department of Hematology and Cancer Prevention School of Public Health in Bytom Medical University of Silesia in Katowice Katowice

Department of Hematology and Oncology Dana Farber Cancer Institute Harvard Medical School Boston MA

Department of Hematology and Oncology Nagoya City University Graduate School of Medical Sciences Nagoya

Department of Hematology Chaim Sheba Medical Center Ramat Gan Sackler Faculty of Medicine Aviv University Aviv

Department of Hematology Hôpital Haut Lévêque Pessac

Department of Internal Medicine Falun General Hospital Falun

Division of Genetics and Epidemiology The Institute of Cancer Research and The Royal Marsden Hospital London

Hematology Department University Hospital Hôtel Dieu Nantes

Hospital Clínic de Barcelona Institut d'Investigacions Biomèdiques August Pi 1 Sunyer University of Barcelona Barcelona

Institute of Hematology Catholic University Fondazione Policlinico Universitario A Gemelli IRCCS Rome

IRCCS Azienda Ospedaliero Universitaria di Bologna Istituto di Ematologia Seràgnoli Dipartimento di Medicina Specialistica Diagnostica e Sperimentale Università degli Studi Bologna

Janssen Research and Development LLC Raritan NJ

Janssen Research and Development LLC Spring House PA

Karolinska Institute Department of Medicine Division of Hematology Karolinska University Hospital at Huddinge Stockholm

Kiev Center for Bone Marrow Transplantation Kiev

Memorial Sloan Kettering Cancer Center New York NY

S P Botkin City Clinical Hospital Moscow Russian Federation

University Hospital of Salamanca IBSAL Cancer Research Center IBMCC Salamanca

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ClinicalTrials.gov
NCT03277105