Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study

• Type of Material: Article
• Authors: Nizar J. Bahlis, University of Calgary; Meletios A. Dimopoulos, National and Kapodistrian University of Athens; Darrell J. White, Dalhousie University; Lotfi Benboubker, Centre Hospitalier Régional Universitaire; Gordon Cook, Leeds Teaching Hospitals NHS Trust; Merav Leiba, Ben Gurion University of the Negev; 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 Hôtel-Dieu; Jonathan Kaufman, Emory University; Maria Krevvata, Janssen Research & Development, LLC; Christopher Chiu, Janssen Research & Development, LLC; Xiang Qin, Janssen Research & Development, LLC; Linda Okonkwo, Janssen Research & Development, LLC; Sonali Trivedi, Janssen Research & Development, LLC; Jon Ukropec, Janssen Global Medical Affairs; Ming Qi, Janssen Research & Development, LLC; Jesus San-Miguel, Clínica Universidad de Navarra
• Language: English
• Date: 2020-01-30
• Publisher: NATURE PUBLISHING GROUP
• Publication Version: Final Published Version
• Copyright Statement: © 2020, The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41375-020-0711-6
• Title of Journal or Parent Work: LEUKEMIA
• Volume: 34
• Issue: 7
• Start Page: 1875
• End Page: 1884
• Grant/Funding Information: This study was sponsored by Janssen Research & Development, LLC.; Medical writing and editorial support were provided by Kristin Runkle, PhD, of MedErgy and were funded by Janssen Global Services, LLC.
• Keywords: Hematology; ANTIBODY DARATUMUMAB; SURVIVAL; Oncology; Science & Technology; BORTEZOMIB; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Oncology; Biophysics, Medical

Abstract

In POLLUX, daratumumab (D) plus lenalidomide/dexamethasone (Rd) reduced the risk of disease progression or death by 63% and increased the overall response rate (ORR) versus Rd in relapsed/refractory multiple myeloma (RRMM). Updated efficacy and safety after >3 years of follow-up are presented. Patients (N = 569) with ≥1 prior line received Rd (lenalidomide, 25 mg, on Days 1–21 of each 28-day cycle; dexamethasone, 40 mg, weekly) ± daratumumab at the approved dosing schedule. Minimal residual disease (MRD) was assessed by next-generation sequencing. After 44.3 months median follow-up, D-Rd prolonged progression-free survival (PFS) in the intent-to-treat population (median 44.5 vs 17.5 months; HR, 0.44; 95% CI, 0.35–0.55; P < 0.0001) and in patient subgroups. D-Rd demonstrated higher ORR (92.9 vs 76.4%; P < 0.0001) and deeper responses, including complete response or better (56.6 vs 23.2%; P < 0.0001) and MRD negativity (10–5; 30.4 vs 5.3%; P < 0.0001). Median time to next therapy was prolonged with D-Rd (50.6 vs 23.1 months; HR, 0.39; 95% CI, 0.31–0.50; P < 0.0001). Median PFS on subsequent line of therapy (PFS2) was not reached with D-Rd versus 31.7 months with Rd (HR, 0.53; 95% CI, 0.42–0.68; P < 0.0001). No new safety concerns were reported. These data support using D-Rd in patients with RRMM after first relapse.