Daratumumab, lenalidomide, and dexamethasone in relapsed/refractory myeloma: a cytogenetic subgroup analysis of POLLUX

• Type of Material: Article
• Authors: Jonathan Kaufman, Emory University; Meletios A. Dimopoulos, National and Kapodistrian University of Athens; Darrell White, Dalhousie University; Lotfi Benboubker, Centre Hospitalier Régional Universitaire; Gordon Cook, Leeds Teaching Hospitals NHS Trust; Merav Leiba, Ben Gurion University of the Negev; James Morton, Icon Cancer Care; P. Joy 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; Heather J. Sutherland, University of British Columbia; Hila Magen, Chaim Sheba Medical Center; Shinsuke Iida, Nagoya City University; Jin Seok Kim, Yonsei University; H. Miles Miles Prince, Epworth HealthCare; Tara Cochrane, Gold Coast University Hospital; Albert Oriol, Hospital Germans Trias I Pujol; Nizar J. Bahlis, University of Calgary; Ajai Chari, Icahn School of Medicine at Mount Sinai; Lisa O'Rourke, Janssen Research & Development; Sonali Trivedi, Janssen Research & Development; Tineke Casneuf, Janssen Research & Development; Maria Krevvata, Janssen Research & Development; Jon Ukropec, Janssen Global Medical Affairs; Rachel Kobos, Janssen Research & Development; Herve Avet-Loiseau, IUC Oncopole; Saad Z. Usmani, Atrium Health; Jesus San-Miguel, Clínica Universidad de Navarra
• Language: English
• Date: 2020-11-03
• Publisher: SPRINGERNATURE
• 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/s41408-020-00375-2
• Title of Journal or Parent Work: BLOOD CANCER JOURNAL
• Volume: 10
• Issue: 11
• Start Page: 111
• End Page: 111
• 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; MULTIPLE-MYELOMA; PROGRESSION-FREE SURVIVAL; Life Sciences & Biomedicine; Oncology; Science & Technology; ANTIBODY DARATUMUMAB
• Research Categories: Health Sciences, Oncology; Health Sciences, Pathology; Health Sciences, Medicine and Surgery

Abstract

High cytogenetic risk abnormalities confer poor outcomes in multiple myeloma patients. In POLLUX, daratumumab/lenalidomide/dexamethasone (D-Rd) demonstrated significant clinical benefit versus lenalidomide/dexamethasone (Rd) in relapsed/refractory multiple myeloma (RRMM) patients. We report an updated subgroup analysis of POLLUX based on cytogenetic risk. The cytogenetic risk was determined using fluorescence in situ hybridization/karyotyping; patients with high cytogenetic risk had t(4;14), t(14;16), or del17p abnormalities. Minimal residual disease (MRD; 10–5) was assessed via the clonoSEQ® assay V2.0. 569 patients were randomized (D-Rd, n = 286; Rd, n = 283); 35 (12%) patients per group had high cytogenetic risk. After a median follow-up of 44.3 months, D-Rd prolonged progression-free survival (PFS) versus Rd in standard cytogenetic risk (median: not estimable vs 18.6 months; hazard ratio [HR], 0.43; P < 0.0001) and high cytogenetic risk (median: 26.8 vs 8.3 months; HR, 0.34; P = 0.0035) patients. Responses with D-Rd were deep, including higher MRD negativity and sustained MRD-negativity rates versus Rd, regardless of cytogenetic risk. PFS on subsequent line of therapy was improved with D-Rd versus Rd in both cytogenetic risk subgroups. The safety profile of D-Rd by cytogenetic risk was consistent with the overall population. These findings demonstrate the improved efficacy of daratumumab plus standard of care versus standard of care in RRMM, regardless of cytogenetic risk.