Daratumumab monotherapy for patients with intermediate-risk or high-risk smoldering multiple myeloma: a randomized, open-label, multicenter, phase 2 study (CENTAURUS)

• Type of Material: Article
• Authors: C. Ola Landgren, Memorial Sloan Kettering Cancer Center; Ajai Chari, Icahn School of Medicine at Mount Sinai; Yael C. Cohen, Tel Aviv University; Andrew Spencer, Monash University; Peter Voorhees, Atrium Health; Jane A. Estell, University of Sydney; Irwindeep Sandhu, University of Alberta; Matthew W. Jenner, Southampton General Hospital; Catherine Williams, Nottingham University Hospital NHS Trust; Michele Cavo, University of Bologna; Niels W. C. J. van de Donk, Vrije Universiteit Amsterdam; Meral Beksac, Ankara University; Philippe Moreau, University Hospital Hôtel-Dieu; Hartmut Goldschmidt, University Hospital Heidelberg; Steven Kuppens, Janssen Research & Development, LLC; Rajesh Bandekar, Janssen Research & Development, LLC; Pamela L. Clemens, Janssen Research & Development, LLC; Tobias Neff, Janssen Research & Development, LLC; Christoph Heuck, Janssen Research & Development, LLC; Ming Qi, Janssen Research & Development, LLC; Craig Hofmeister, Emory University
• Language: English
• Date: 2020-02-05
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41375-020-0718-z
• Title of Journal or Parent Work: Leukemia
• Volume: 34
• Issue: 7
• Start Page: 1840
• End Page: 1852
• Grant/Funding Information: Medical writing and editorial support were provided by Kimberly Carmony, PhD (MedErgy), and were funded by Janssen Global Services, LLC.; This study (ClinicalTrials.gov identifier: NCT02316106) was funded by Janssen Research & Development, LLC.; COL was supported by Memorial Sloan Ketteringʼs Core Grant (P30 CA008748).; CCH was supported by Winship Cancer Institute’s Core Grant (P30 CA138292).
• Keywords: Bone-marrow; Oncology; Pharmacokinetics; Targeting CD38; Life Sciences & Biomedicine; Monoclonal gammopathy; Criteria; Antibody daratumumab; Science & Technology; Hematology; Progression
• Research Categories: Health Sciences, Oncology; Health Sciences, Immunology; Biology, Cell; Health Sciences, Pharmacology

Abstract

Current guidelines for smoldering multiple myeloma (SMM) recommend active monitoring until the onset of multiple myeloma (MM) before initiating treatment or enrollment in a clinical trial. Earlier intervention may delay progression to MM. In CENTAURUS, 123 patients with intermediate-risk or high-risk SMM were randomly assigned to daratumumab 16 mg/kg intravenously on extended intense (intense), extended intermediate (intermediate), or short dosing schedules. At the prespecified primary analysis (15.8-month median follow-up), the complete response (CR) rates (co-primary endpoint) were 2.4%, 4.9%, and 0% for intense, intermediate, and short dosing, respectively; the co-primary endpoint of CR rate >15% was not met. Progressive disease (PD)/death rates (number of patients who progressed or died divided by total duration of progression-free survival [PFS] in patient-years; co-primary endpoint) for intense, intermediate, and short dosing were 0.055 (80% confidence interval [CI], 0.014–0.096), 0.102 (80% CI, 0.044–0.160), and 0.206 (80% CI, 0.118–0.295), respectively, translating to a median PFS ≥24 months in all arms (P < 0.0001, <0.0001, and =0.0213, respectively).