Efficacy and Safety of Anselamimab in Immunoglobulin Light Chain Amyloidosis: Results From the Randomized CARES Trials
Year: 2026
Type: article
Study design: Clinical Trial
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.
Source: Journal of Clinical Oncology
DOI: 10.1200/jco-26-00755
Authors: Ashutosh D. Wechalekar, Angela Dispenzieri, Vaishali Sanchorawala, Efstathios Kastritis, Divaya Bhutani, Giada Bianchi, Victor H. Jimenez-Zepeda, Kenshi Suzuki, Suzanne Lentzsch, Antoine Huart, Alexander Carpinteiro, Eugene Scott Swenson, Zilehuma Khan, Julia Catini, Hrishikesh Kulkarni, Brian Meltzer, Stephen Lake, Michaela Liedtke, for the CARES Investigators, Stephen Bek Ngie Ting, Peter Norman Mollee, Hermine Agis, Irene Strassl, Nathalie Meuleman, Michel Delforge, Victor Jimenez Zepeda, Shuyang Zhang, Xin Du, Jianan Wang, Honglan Qian, Chunyan Sun, Honglan Qian, Chunyan Sun, Frantisek Sedlak, Arnaud Jaccard, Karim Belhadj, Bertrand Arnulf, Lionel Karlin, Margaret Macro, Jean-Marc Schiano De Colella, Anne-Marie Stoppa, Frank Bridoux, Thomas Chalopin, Jean-Francois Viallard, Antoine Huart, Alexander Carpinteiro, Roland Fenk, Timon Hansen, Vera Girke, Axel Nogai, Efstathios Kastritis, Argiris (Anargyros) Symeonidis, Moshe Gatt, Noa Lavi, Hila Magen, Giovanni Palladini, Ombretta Annibali, Fabrizio Pane, Gabriele Buda, Tadao Ishida, Kenshi Suzuki, Shinsuke Iida, Takayuki Ikezoe, Krzysztof Jamroziak, Jamin Byun, Youngil Koh, Kihyun Kim, Ramon Lecumberri Villamediana, Maria Teresa Cibeira Lopez, Irene Romera Martinez, Rafael F. Duarte, Rafael Rios, Isabel Angela Krsnik Castello, Maria Esther Gonzalez Garcia, Eusebio Narciso Martin Chacon, Javier Alberto Rojas Martinez, Ashutosh Wechalekar, Jason Valent, Michaela Liedtke, Michael A. Rosenzweig, Alfred Chung, Sandy Wong, Naresh Bumma, Divaya Bhutani, Giada Bianchi, Raymond Comenzo, Mahmoud Gaballa, Hans C. Lee, Gregory P. Kaufman, Eva Medvedova, Frank Passero, Keith Stockerl-Goldstein, Adam Waxman, Vaishali Sanchorawala, Anita D'Souza, Andrew Cowan, Sarah Lee, Edward Libby, Angela Dispenzieri, Amandeep Godara, Tibor Kovacsovics, Salyka M. Sengsayadeth, Stacey Ann Goodman, Chakra Chaulagain
Institutions: University College London, Mayo Clinic, Boston University, Boston Medical Center, National and Kapodistrian University of Athens, Columbia University Irving Medical Center, Columbia University, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Dana-Farber Brigham Cancer Center, Weill Cornell Medicine, Japanese Red Cross Medical Center, Herbert Irving Comprehensive Cancer Center, Centre Hospitalier Universitaire de Toulouse, Essen University Hospital, Stiftung Universitätsmedizin Essen, University of Duisburg-Essen, AstraZeneca (United States), Stanford Medicine, Stanford University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W7162806478