Amyloidosis: Pathogenesis and New Therapeutic Options

Abstract

The systemic amyloidoses are a group of complex diseases caused by tissue deposition of misfolded proteins that results in progressive organ damage. The most common type, immunoglobulin light chain amyloidosis (AL), is caused by clonal plasma cells that produce misfolded light chains. The purpose of this review is to provide up-to-date information on diagnosis and treatment options for AL amyloidosis. Early, accurate diagnosis is the key to effective therapy, and unequivocal identification of the amyloidogenic protein may require advanced technologies and expertise. Prognosis is dominated by the extent of cardiac involvement, and cardiac staging directs the choice of therapy. Treatment for AL amyloidosis is highly individualized, determined on the basis of age, organ dysfunction, and regimen toxicities, and should be guided by biomarkers of hematologic and cardiac response. Alkylator-based chemotherapy is effective in almost two thirds of patients. Novel agents are also active, and trials are ongoing to establish their optimal use. Treatment algorithms will continue to be refined through controlled trials. Advances in basic research have led to the identification of new drug targets and therapeutic approaches, which will be integrated with chemotherapy in the future.