Daratumumab-Bortezomib-Cyclophosphamide-Dexamethasone in Newly Diagnosed Amyloidosis: ANDROMEDA Final Survival Analysis
Abstract
In the primary analysis of ANDROMEDA, addition of subcutaneous daratumumab to bortezomib/cyclophosphamide/dexamethasone (D-VCd) significantly improved hematologic complete response (CR) rate versus VCd, establishing D-VCd as the only approved therapy for light-chain (AL) amyloidosis. We present results from the preplanned final analysis. In this phase 3 trial, we randomly assigned 388 patients with newly diagnosed AL amyloidosis to six cycles of VCd alone (control group) or with subcutaneous daratumumab (D-VCd) followed by single-agent daratumumab every 4 weeks for up to 24 total cycles. The primary endpoint was hematologic CR. The updated hematologic CR rate was 59.5% for D-VCd versus 19.2% for VCd (odds ratio, 6.03; 95% confidence interval [CI], 3.80-9.58; P<0.0001). Median time to hematologic CR was shorter with D-VCd (67.5 days [range, 8.0-879.0]) versus VCd (85.0 days [range, 14.0-617.0]). With a median follow-up of 61.4 months, significant improvement was observed with D-VCd versus VCd in major organ deterioration-progression-free survival (hazard ratio, 0.44; 95% CI, 0.31-0.63; P<0.0001) and overall survival (hazard ratio, 0.62; 95% CI, 0.42-0.90; P=0.0121). Cardiac and renal response rates were 2-3 times higher with D-VCd versus VCd. Achieving hematologic or cardiac CR was associated with improved major organ deterioration-progression-free survival and overall survival. Adverse events were consistent with the known safety profiles for VCd and daratumumab. Adding daratumumab to VCd resulted in deeper and more rapid hematologic responses and recovery of organ function, translating to statistically significant improvement in both overall survival and major organ deterioration-progression-free survival in newly diagnosed AL amyloidosis. ClinicalTrials.gov NCT03201965.
Article Details
Authors (45)
Efstathios Kastritis
Giovanni Palladini
Department of Molecular Medicine, University of Pavia, Italy (M.N., G.D.S., G.P.).
Monique C Minnema
UMC Utrecht, Utrecht, Netherlands
Ashutosh D. Wechalekar
National Amyloidosis Centre, University College London, Royal Free Hospital, London, United Kingdom.
Arnaud Jaccard
Hans C Lee
Sarah Cannon Research Institute, Nashville, Tennessee, United States
Vaishali Sanchorawala
Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, Boston, Massachusetts, United States
Peter Mollee
10Department of Haematology, Princess Alexandra Hospital and University of Queensland, Brisbane, Australia
Jin Lu
Center for Biological Physics, Arizona State University
Stefan O. Schönland
Heidelberg University, Heidelberg, Germany
Moshe E Gatt
Hadassah Medical Center, jerusalem, Israel
Kenshi Suzuki
Kihyun Kim
Division of Hematology–Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea
M Teresa Cibeira
Hospita Clinic de Barcelona, Barcelona, Spain
Manisha Bhutani
Atrium Health Levine Cancer Institute, Charlotte, North Carolina, United States
Meral Beksac
Edward N. Libby
Fred Hutchinson Cancer Research Center, San Diego, California, United States
Jason Valent
Cleveland Clinic Foundation, Cleveland, Ohio, United States
Vania Hungria
Clinica São Germano, São Paulo
Michael A Rosenzweig
City of Hope, Duarte, California, United States
Naresh Bumma
Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, United States
Antoine Huart
Department of Nephrology and Transplantation, Toulouse Amyloidosis Center, Toulouse, France
Meletios-Athanasios A. Dimopoulos
Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece, Department of Medicine, Korea University, Seoul, Republic of Korea, Athens, Greece
Divaya Bhutani
Columbia University Medical Center, New York
Adam Waxman
University of Pennsylvania, Philadelphia, Pennsylvania, United States
Stacey Goodman
Vanderbilt University, Nashville, Tennessee, United States
Jeffrey A. Zonder
Selay Lam
London Health Sciences Centre
Kevin W. Song
The Vancouver General Hospital, Vancouver, Canada
Timon Hansen
Onkologicum HOPA, Hamburg, Hamburg, Germany
Salomon Manier
Wilfried W.H. Roeloffzen
Amyloidosis Centre of Expertise Department of Internal Medicine, Faculty of Medical Sciences, University Medical Center Groningen, Groningen, Netherlands
Krzysztof Jamroziak
Medical University of Warsaw, Warsaw, Poland
Fiona Kwok
Westmead Hospital, Westmead, Australia
Chihiro Shimazaki
Japan Community Health care Organization Kyoto Kuramaguchi Medical Center, Kyoto, Japan
Jin-Seok Kim
Yonsei University College of Medicine, Seoul, Korea, Republic of
Edvan de Queiroz Crusoé
Hospital Universitário Professor Edgar Santos (HUPES), Universidade Federal da Bahia; Clinica CEHON Rede D'or Oncologia, Salvador, Brazil
NamPhuong Tran
Janssen Research & Development, LLC, Los Angeles, California, United States
Jianping Wang
Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering
Yuping Chen
Sandra Y. Vasey
Johnson & Johnson, Spring House, PA
Jordan M Schecter
Janssen Research & Development, LLC, Raritan, New Jersey, United States
Jessica Vermeulen
Janssen Research & Development, LLC, Leiden, Netherlands
Raymond Comenzo
Tufts Medical Center, Boston, Massachusetts, United States
Giampaolo Merlini
From the Amyloidosis Research Center, Foundation IRCCS Policlinico San Matteo, Department of Molecular Medicine, University of Pavia, Pavia, Italy.