Diagnosis and treatment of AL amyloidosis in 2022

Abstract

Light chain (AL) amyloidosis is a rare, progressive and typically fatal disease (when advanced) characterized by organ dysfunction secondary to deposition of misfolded fibrils of immunoglobulin light chains that are produced by clonal plasma cells or B cells. Although less than 10% of AL patients qualify for CRAB criteria of symptomatic myeloma (Calcium elevation, Renal dysfunction, Anemia, and Bone disease), the majority of these patients have significant impairment of vital organs, such as the heart, kidney and liver. This implies that the common risk factors used for the assessment of multiple myeloma (MM) are not applicable to AL. AL amyloidosis affects 8–12 individuals per million person-years, and its clinical presentation is variable depending on the extent and number of vital organs affected. The locations of amyloid deposits can vary among patients, thus contributing to the heterogeneity of the clinical manifestations. The heart and kidney, which are the most affected organs, can lead to renal failure, cardiomyopathy, and pericardial and pleural effusions. Initial symptoms at onset are often non-specific (e.g., weight loss, fatigue). Despite advances in the diagnostic tools and treatment options, early mortality rates remain high; the expected one-year mortality is approximately 30%. Unfortunately, by the time the AL diagnosis is made, and treatment is initiated, the disease has often become advanced.