Efficacy and Safety of Anselamimab in Immunoglobulin Light Chain Amyloidosis: Results From the Randomized CARES Trials
Abstract
PURPOSE In immunoglobulin light chain (AL) amyloidosis, amyloid fibrils cause organ dysfunction. Anselamimab, a monoclonal antibody, selectively binds to amyloid fibrils, accelerating their clearance. METHODS Newly diagnosed patients with European modification of Mayo 2004 stage IIIa or IIIb AL amyloidosis were randomly assigned to receive anselamimab or placebo with cyclophosphamide, bortezomib, and dexamethasone (with or without daratumumab). The primary end point was a hierarchical composite of time to all-cause mortality (ACM) and frequency of cardiovascular hospitalizations (CVHs), analyzed using the Finkelstein-Schoenfeld test and win ratio estimation. RESULTS Among 406 randomly assigned patients, the primary end point win ratio for anselamimab versus placebo was 1.11 (95% CI, 0.83, 1.50; P = .332) and the hazard ratio (HR) for ACM was 0.80 (95% CI, 0.57, 1.13; P = .290). CVH rates in the anselamimab and placebo groups were 0.59 (95% CI, 0.42, 0.83) and 0.89 (95% CI, 0.55, 1.43), respectively ( P = .145). Among patients with kappa isotype (n = 72), the win ratio was 2.06 (95% CI, 0.98, 4.31; P = .100) and anselamimab reduced ACM by 62% versus placebo (HR, 0.38; 95% CI, 0.17 to 0.86; nominal P = .012), and CVH by 71% (IRR, 0.29; 95% CI, 0.10 to 0.87; nominal P = .028) with improvements in Kansas City Cardiomyopathy Questionnaire-Overall Score. There was no clinical benefit observed in the lambda population. Anselamimab was generally well-tolerated; safety data were comparable between treatment arms overall. CONCLUSION Treatment with anselamimab, an antifibril antibody used alongside antiplasma cell dyscrasia therapy, while not meeting the primary end point in the overall population, significantly improved ACM and CVH in patients with kappa AL, potentially offering a new therapeutic option for this isotype.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (92)
Ashutosh D. Wechalekar
National Amyloidosis Centre, University College London, Royal Free Hospital, London, United Kingdom.
Victor H. Jimenez-Zepeda
Suzanne Lentzsch
Columbia University Medical Center, New York, New York, United States
Eugene Scott Swenson
Zilehuma Khan
Julia Catini
Hrishikesh Kulkarni
UCLA
Brian Meltzer
Stephen Lake
Stephen Bek Ngie Ting
Peter Norman Mollee
Hermine Agis
Medical University of Vienna, Vienna
Irene Strassl
20Ordensklinikum Linz, Linz, Austria
Nathalie Meuleman
7Jules Bordet Institute, Hematology Department, Brussels, Belgium
Michel Delforge
Victor Jimenez Zepeda
Shuyang Zhang
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine
Xin Du
State Key Laboratory of Immune Response and Immunotherapy, Department of Rheumatology and Immunology, The First Affiliated Hospital of University of Science and Technology of China, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China
Jianan Wang
Honglan Qian
1The First Affiliated Hospital of Wenzhou Medical University, Department of Hematology, Wenzhou, China
Chunyan Sun
School of Mathematics and Physics, Anqing Normal University 1 , Anqing 246133,
František Sedlák
Arnaud Jaccard
Karim Belhadj
7Department of Hematology, Créteil Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France
Bertrand Arnulf
Hôpital Universitaire St. Louis, Assistance Publique–Hôpitaux de Paris (AP-HP), Paris
Lionel Karlin
Service Hématologie, Hôpital Universitaire Lyon Sud, Pierre-Bénite, France
Margaret Macro
Service Hématologie, Institut Hématologie de Basse Normandie, Hôpital Universitaire de Caen, Caen, France
Jean-Marc Schiano De Colella
4Département Hématologie, Institut Paoli Calmettes, Marseille, France
Anne-Marie Stoppa
Frank Bridoux
Thomas Chalopin
Jean-Francois Viallard
4Bordeaux University Hospital, Bordeaux, France
Antoine Huart
Department of Nephrology and Transplantation, Toulouse Amyloidosis Center, Toulouse, France
Alexander Carpinteiro
Roland Fenk
4University Hospital Düsseldorf, Department of Hematology, Oncology and Clinical Immunology, Düsseldorf, Germany
Timon Hansen
Onkologicum HOPA, Hamburg, Hamburg, Germany
Vera Girke
Axel Nogai
Efstathios Kastritis
Argiris (Anargyros) Symeonidis
Moshe Gatt
Hadassah Medical Cener, Hebrew University of Jerusalem, Jerusalem, Israel
Noa Lavi
Department of Hematology, Rambam Health Care Campus, Haifa 3109601, Israel
Hila Magen
Chaim Sheba Medical Center, Ramat-Gan, Israel
Giovanni Palladini
Department of Molecular Medicine, University of Pavia, Italy (M.N., G.D.S., G.P.).
Ombretta Annibali
Policlinico Universitario Campus Bio-Medico, Dipartimento di Medicina e Chirurgia Università Campus Bio-Medico, Rome
Fabrizio Pane
4Hematology – Department of Clinical Medicine and Surgery, University Hospital “Federico II”, Napoli, Italy
Gabriele Buda
Department of Clinical and Experimental Medicine, Hematology, University of Pisa, Pisa, Italy
Tadao Ishida
Japanese Red Cross Medical Center, Tokyo
Kenshi Suzuki
Shinsuke Iida
Takayuki Ikezoe
3Fukushima Medical University School of Medicine, Hematology, Fukushima, Japan
Krzysztof Jamroziak
Medical University of Warsaw, Warsaw, Poland
Jamin Byun
Youngil Koh
Seoul National University Hospital, Seoul National University, Jongno-gu, Seoul, South Korea
Kihyun Kim
Division of Hematology–Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea
Ramon Lecumberri Villamediana
Maria Teresa Cibeira López
1Hospital Clinic of Barcelona, Barcelona, Spain
Irene Romera Martinez
Rafael F. Duarte
Rafael Ríos
7Hospital Universitario Puerta de Hierro, Majadahonda, Spain
Isabel Angela Krsnik Castello
María Esther Gonzalez García
26Hematology Department, Hospital Universitario de Cabueñes, Gijon, Spain
Eusebio Narciso Martin Chacon
Javier Alberto Rojas Martinez
Ashutosh Wechalekar
National Amyloidosis Centre, London, United Kingdom
Jason Valent
Cleveland Clinic Foundation, Cleveland, Ohio, United States
Michaela Liedtke
Michael A. Rosenzweig
Alfred Chung
6University of California San Francisco, San Francisco, United States
Sandy Wong
10Bristol Myers Squibb, Princeton, United States
Naresh Bumma
Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, United States
Divaya Bhutani
Columbia University Medical Center, New York
Giada Bianchi
Raymond Comenzo
Tufts Medical Center, Boston, Massachusetts, United States
Mahmoud Gaballa
4The University of Texas MD Anderson Cancer Center, Houston, United States
Hans C. Lee
1Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
Gregory P. Kaufman
Eva Medvedova
Knight Cancer Institute, Oregon Health and Science University, Portland
Frank Passero
Keith Stockerl-Goldstein
1Washington University School of Medicine, Division of Oncology, Department of Medicine, Saint Louis, United States
Adam Waxman
University of Pennsylvania, Philadelphia, Pennsylvania, United States
Vaishali Sanchorawala
Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, Boston, Massachusetts, United States
Anita D'Souza
1Medical College of Wisconsin, Milwaukee, United States
Andrew Cowan
3University of Washington and Fred Hutchinson Cancer Center, Seattle, United States
Sarah Lee
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA
Edward Libby
3University of California, San Diego, San Diego, United States
Angela Dispenzieri
Amandeep Godara
University of Utah School of Medicine, Salt Lake City, Utah, United States
Tibor Kovacsovics
9City of Hope, Goodyear, United States
Salyka M. Sengsayadeth
Stacey Ann Goodman
Chakra Chaulagain
Department of Hematology and Oncology, Myeloma and Amyloidosis Program, Cleveland Clinic Florida, Weston