Prognostic factors and progression biomarkers in AL amyloidosis: mapping current knowledge and critical gaps
Abstract
Abstract The therapeutic landscape for systemic immunoglobulin light chain (AL) amyloidosis has been revolutionized by daratumumab-based regimens, achieving 76% 5-year overall survival in the landmark ANDROMEDA trial. However, the current prognostic models were developed using patient populations treated with now-suboptimal therapies, creating a critical gap between risk stratification models and contemporary outcomes. This comprehensive review analyzes prognostic factors and progression biomarkers in AL, categorizing them into disease-specific (clone-related and organ-related) and patient-specific factors. Notably, traditional baseline biomarkers including difference between involved and uninvolved free light chains and bone marrow plasma cell burden are losing prognostic significance with effective clone-directed therapies. Emerging approaches show promise, including dynamic markers such as minimal residual disease by free light chain mass spectrometry, cardiac imaging parameters such as global longitudinal strain, and functional measures. There is an urgent need for validation studies and prognostic model refinement to identify patients at high risk who may benefit from interventions beyond anti–plasma cell therapy.
Article Details
Authors (20)
Rajshekhar Chakraborty
1Department of Medicine, Columbia University Irving Medical Center, New York, NY
Yevgeniy Brailovsky
Columbia University Irving Medical Center, New York, New York, United States
Mazen Hanna
Department of Cardiovascular Medicine, Heart, Vascular & Thoracic Institute, Cleveland Clinic, OH.
Ronald Witteles
Stanford University, Stanford, California, United States
Joban Vaishnav
4Department of Medicine, Johns Hopkins University, Baltimore, MD
James Edward Hoffman
5Department of Medicine, University of Miami Sylvester Cancer Center, Miami, FL
Jan Griffin
Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, United States
Pablo Garcia-Pavia
Department of Cardiology, Hospital Universitario Puerta de Hierro, Instituto de Investigación Sanitaria Puerta de Hierro–Segovia de Arana, Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares, and Centro Nacional de Investigaciones Cardiovasculares, Madrid
David Wolinsky
8Department of Nuclear Medicine, Cleveland Clinic, Weston, FL
Chafic Karam
9Department of Neurology, University of Pennsylvania, Philadelphia, PA
Helen Lachmann
Royal Free London NHS Foundation Tr, London, United Kingdom
Morie Gertz
11Division of Hematology, Mayo Clinic, Rochester, MN
Brian Boursiquot
Columbia University Medical Center, New York, New York, United States
Dimitrios Bampatsias
Clinical Cardiovascular Research Laboratory for the Elderly (CCRLE), New York-Presbyterian/Columbia University Irving Medical Center, New York, NY (S.T., D.B., M.S.M.).
Kristen Hsu
13Amyloidosis Research Consortium, Newton, MA
Phaedra Johnson
13Amyloidosis Research Consortium, Newton, MA
Jamie Zigterman
13Amyloidosis Research Consortium, Newton, MA
Ana Carolina Kazemzadeh
13Amyloidosis Research Consortium, Newton, MA
Mathew S. Maurer
Ashutosh Wechalekar
National Amyloidosis Centre, London, United Kingdom