Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX

• Type of Material: Article
• Authors: Meletios A. Dimopoulos, University of Athens; Jesus San-Miguel, Clinica Universidad de Navarra; Andrew Belch, University of Alberta; Darrell White, Dalhousie University; Lotfi Benboubker, Centre Hospitalier Regional Universitaire; Gordon Cook, Leeds Teaching Hospitals NHS Trust; Merav Leiba, Sheba Medical Center; James Morton, Icon Cancer Care; P. Joy Ho, Royal Prince Alfred Hospital; Kihyun Kim, Sungkyunkwan University; Naoki Takezako, National Hospital Organization Disaster Medical Center of Japan; Philippe Moreau, University Hospital Hotel-Dieu; Jonathan Kaufman, Emory University; Heather J. Sutherland, University of British Columbia; Marc Lalancette, Laval University; Hila Magen, Rabin Medical Center; Shinsuke Iida, Nagoya City University; Jin Seok Kim, Yonsei University; H. Miles Prince, University of Melbourne; Tara Cochrane, Gold Coast University Hospital; Albert Oriol, Hospitals Germans Trias; Nizar J. Bahlis, University of Calgary; Ajai Chari, Icahn School of Medicine at Mount Sinai; Lisa O'Rourke, Janssen Research & Development, LLC; Kaida Wu, Janssen Research & Development, LLC; Jordan M. Schecter, Janssen Research & Development, LLC; Tineke Casneuf, Janssen Research & Development, LLC; Christopher Chiu, Janssen Research & Development, LLC; David Soong, Janssen Research & Development, LLC; A. Kate Sasser, Genmab US Inc; Nushmia Z. Khokhar, Janssen Research & Development, LLC; Herve Avet-Loiseau, IUC Oncopole; Saad Z. Usmani, Atrium Health
• Language: English
• Date: 2018-11-30
• Publisher: Ferrata Storti Foundation
• Publication Version: Final Published Version
• Copyright Statement: © 2018 Ferrata Storti Foundation.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3324/haematol.2018.194282
• Title of Journal or Parent Work: Haematologica
• ISSN: 0390-6078
• Volume: 103
• Issue: 12
• Start Page: 2088
• End Page: 2096
• Grant/Funding Information: This study was sponsored by Janssen Research & Development, LLC.; The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at https://www.janssen.com/clinical-trials/transparency.
• Keywords: Life Sciences & Biomedicine; Science & Technology; Hematology; ANTIBODY DARATUMUMAB; CRITERIA
• Research Categories: Health Sciences, Oncology; Chemistry, Pharmaceutical

Abstract

In the POLLUX study, daratumumab plus lenalidomide/dexamethasone significantly reduced risk of progression/death versus lenalidomide/ dexamethasone alone in relapsed/refractory multiple myeloma. We provide one additional year of follow up and include the effect on minimal residual disease and in clinically relevant subgroups. After 25.4 months of follow up, daratumumab plus lenalidomide/dexamethasone prolonged progression-free survival versus lenalidomide/dexamethasone alone (median not reached vs. 17.5 months; hazard ratio, 0.41; 95% confidence interval, 0.31-0.53; P<0.0001). The overall response rate was 92.9% versus 76.4%, and 51.2% versus 21.0% achieved a complete response or better, respectively (both P<0.0001). At the 10–5 sensitivity threshold, 26.2% versus 6.4% were minimal residual disease–negative, respectively (P<0.0001). Post hoc analyses of clinically relevant patient subgroups demonstrated that progression-free survival was significantly prolonged for daratumumab plus lenalidomide/dexamethasone versus lenalidomide/dexamethasone regardless of number of prior lines of therapy. Patients previously treated with lenalidomide or thalidomide and those refractory to bortezomib received similar benefits (all P<0.01). Treatment benefit with daratumumab plus lenalidomide/dexamethasone was maintained in high-risk patients (median progression-free survival 22.6 vs. 10.2 months; hazard ratio, 0.53; 95% confidence interval, 0.25-1.13; P=0.0921) and patients with treatment-free intervals of >12 and ≤12 months and >6 and ≤6 months. No new safety signals were observed. In relapsed/refractory multiple myeloma patients, daratumumab plus lenalidomide/dexamethasone continued to improve progression-free survival and deepen responses versus lenalidomide/dexamethasone.