Systemic
immunoglobulin light chain amyloidosis is a
protein misfolding disease caused by the conversion of
immunoglobulin light chains from their soluble functional states into highly organized
amyloid fibrillar aggregates that lead to organ dysfunction. The disease is progressive and, accordingly, early diagnosis is vital to prevent irreversible organ damage, of which cardiac damage and renal damage predominate. The development of novel sensitive
biomarkers and imaging technologies for the detection and quantification of organ involvement and damage is facilitating earlier diagnosis and improved evaluation of the efficacy of new and existing
therapies. Treatment is guided by risk assessment, which is based on levels of cardiac
biomarkers; close monitoring of clonal and organ responses guides
duration of therapy and changes in regimen. Several new classes of drugs, such as
proteasome inhibitors and
immunomodulatory drugs, along with high-dose
chemotherapy and autologous haematopoietic
stem cell transplantation, have led to rapid and deep suppression of
amyloid light chain production in the majority of patients. However, effective
therapies for patients with advanced cardiac involvement are an unmet need. Passive
immunotherapies targeting clonal plasma cells and directly accelerating removal of
amyloid deposits promise to further improve the overall outlook of this increasingly treatable disease.