Efficacy and Safety of Anselamimab in Immunoglobulin Light Chain Amyloidosis: Results From the Randomized CARES Trials

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.

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Journal
Journal of Clinical Oncology
Published
2026-05-29
DOI
https://doi.org/10.1200/jco-26-00755
Primary Topic
Amyloidosis: Diagnosis, Treatment, Outcomes
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article
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article

Efficacy and Safety of Anselamimab in Immunoglobulin Light Chain Amyloidosis: Results From the Randomized CARES Trials

Ramón Lecumberri Villamediana, Brian Meltzer, Hermine Agis, Gabriele Buda et al.
Journal of Clinical Oncology
Amyloidosis: Diagnosis, Treatment, Outcomes
article

Efficacy and Safety of Anselamimab in Immunoglobulin Light Chain Amyloidosis: Results From the Randomized CARES Trials

Ramón Lecumberri Villamediana, Brian Meltzer, Hermine Agis, Gabriele Buda, Ombretta Annibali, Alexander Carpinteiro, Arnaud Jaccard, Naresh Bumma, Suzanne Lentzsch, Hila Magen, Eva Medvedova, Takayuki Ikezoe, Amandeep Godara, Rafael Ríos, František Sedlák, Eugene Swenson, Timon Hansen, Irene Straßl, Axel Nogai, Karim Belhadj, Thomas Chalopin, Giada Bianchi, Michaela Liedtke, Julia Catini, Rafael Duarte, Jamin Byun, Frank Bridoux, Javier Alberto Rojas Martínez, Divaya Bhutani, Antoine Huart, Irene Romera Martínez, Keith Stockerl-Goldstein, Victor H. Jimenez- Zepeda, Victor Jimenez Zepeda, Moshe Gatt, Argiris Symeonidis, Jason Valent, Adam Waxman, Maria Teresa Cibeira Lopez, Anita D'Souza, Stephen Lake, Nathalie Meuleman, Efstathios Kastritis, Michel Delforge, Honglan Qian, Sandy Wong, Giovanni Palladini, Krzysztof Jamroziak, for the CARES Investigators, Jianan Wang, Vaishali Sanchorawala, Chunyan Sun, Kenshi Suzuki, Gregory P. Kaufman, Peter Norman Mollee, Lionel Karlin, Stephen Bek Ngie Ting, Ashutosh D. Wechalekar, Kihyun Kim, Noa Lavi, Raymond Comenzo, Mahmoud Gaballa, Zilehuma Khan, Vera Girke, Isabel Angela Krsnik Castello, Roland Fenk, Sarah Lee, Anne-Marie Stoppa, Jean-Francois Viallard, Hrishikesh Kulkarni, Eusebio Narciso Martin Chacon, Frank Passero, Fabrizio Pane, Angela Dispenzieri, Margaret Macro, Andrew Cowan, Jean-Marc Schiano De Colella, Hans C. Lee, Michael A. Rosenzweig, Youngil Koh, Bertrand Arnulf, Alfred Chung, Tadao Ishida, Maria Esther Gonzalez Garcia, Edward Libby, Shinsuke Iida, Xin Du, Shuyang Zhang
article en

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.

Journal of Clinical Oncology
Boston University (US), Boston Medical Center (US), Palo Alto University (US), National and Kapodistrian University of Athens (GR), Cornell University (US), Columbia University Irving Medical Center (US), Japanese Red Cross Medical Center (JP), Amyloidosis Foundation (US), Essen University Hospital (DE), Mayo Clinic in Arizona (US), AstraZeneca (Poland) (PL), Stanford Medicine (US), Dana-Farber Brigham Cancer Center (US), Institute of Molecular Biology (DE), University College London (GB), Alexion Pharma (Switzerland) (CH), University of Duisburg-Essen (DE), Stanford University (US)
Good health and well-being
Openalex Percentile: Top 8%
Amyloidosis: Diagnosis, Treatment, Outcomes
DOIOpen Access PDFOpenAlex
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