Evaluation of Sustained Minimal Residual Disease Negativity With Daratumumab-Combination Regimens in Relapsed and/or Refractory Multiple Myeloma: Analysis of POLLUX and CASTOR

• Type of Material: Article
• Authors: Sagar Lonial, Emory University; Hervé Avet-Loiseau, Unite de Genomique du Myelome; Jesus San-Miguel, Clínica Universidad de Navarra-CIMA; Tineke Casneuf, Janssen Res & Dev; Shinsuke Iida, Nagoya City University; Sagar Z Usmani, Atrium Hlth; Andrew Spencer, Monash University; Philippe Moreau, University Hospital Hôtel-Dieu; Torben Plesner, Vejle Hospital and University of Southern Denmark; Katja Weisel, University Medical Center of Hamburg-Eppendorf; Jon Ukropec, Janssen Scientific Affairs, LLC; Christopher Chiu, Janssen Research & Development, LLC; Sonali Trivedi, Janssen Research & Development, LLC; Himal Amin, Janssen Research & Development, LLC; Maria Krevvata, Janssen Research & Development, LLC; Priya Ramaswami, Janssen Research & Development, LLC; Xiang Qin, Janssen Research & Development, LLC; Mia Qi, Janssen Research & Development, LLC; Steven Sun, Janssen Research & Development, LLC; Ming Qi, Janssen Research & Development, LLC; Rachel Kobos, Janssen Research & Development, LLC; Nizar J Bahlis, University of Calgary
• Language: English
• Date: 2021-04-01
• Publisher: LIPPINCOTT WILLIAMS & WILKINS
• Publication Version: Final Published Version
• Copyright Statement: © 2021 by American Society of Clinical Oncology
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.20.01814
• Title of Journal or Parent Work: JOURNAL OF CLINICAL ONCOLOGY
• Volume: 39
• Issue: 10
• Start Page: 1139
• End Page: +
• Grant/Funding Information: This trial was supported by Janssen Research and Development, LLC.
• Keywords: OUTCOMES; Oncology; DEXAMETHASONE; CRITERIA; ANTIBODY DARATUMUMAB; BORTEZOMIB; Science & Technology; Life Sciences & Biomedicine; LENALIDOMIDE
• Research Categories: Health Sciences, Oncology

Abstract

PURPOSE In relapsed and/or refractory multiple myeloma, daratumumab reduced the risk of progression or death by . 60% in POLLUX (daratumumab/lenalidomide/dexamethasone [D-Rd]) and CASTOR (daratumumab/bortezomib/dexamethasone [D-Vd]). Minimal residual disease (MRD) is a sensitive measure of disease control. Sustained MRD negativity and outcomes were evaluated in these studies. METHODS MRD was assessed via next-generation sequencing (1025) at suspected complete response (CR), 3 and 6 months following confirmed CR (POLLUX), 6 and 12 months following the first dose (CASTOR), and every 12 months post-CR in both studies. Sustained MRD negativity ($ 6 or $ 12 months) was evaluated in the intention-to-treat (ITT) and $ CR populations. RESULTS The median follow-up was 54.8 months in POLLUX and 50.2 months in CASTOR. In the ITT population, MRD-negativity rates were 32.5% versus 6.7% for D-Rd versus lenalidomide and dexamethasone (Rd) and 15.1% versus 1.6% for D-Vd versus bortezomib and dexamethasone (Vd; both P, .0001). Higher MRD negativity rates were achieved in $ CR patients in POLLUX (D-Rd, 57.4%; Rd, 29.2%; P 5 .0001) and CASTOR (D-Vd, 52.8%; Vd, 17.4%; P 5 .0035). More patients in the ITT population achieved sustained MRD negativity $ 6 months with D-Rd versus Rd (20.3% v 2.1%; P, .0001) and D-Vd versus Vd (10.4% v 1.2%; P, .0001), and $ 12 months with D-Rd versus Rd (16.1% v 1.4%; P, .0001) and D-Vd versus Vd (6.8% v 0%). Similar results for sustained MRD negativity were observed among $ CR patients. More patients in the daratumumab-containing arms achieved MRD negativity and sustained MRD negativity, which were associated with prolonged progression-free survival. CONCLUSION Daratumumab-based combinations induce higher rates of sustained MRD negativity versus standard of care, which are associated with durable remissions and prolonged clinical outcomes.