Recent Advances in the Diagnosis, Risk Stratification, and Management of Systemic Light-Chain Amyloidosis

Abstract

The term amyloidosis refers to a group of disorders in which protein fibrils accumulate in certain organs, disrupt their tissue architecture, and impair the function of the effected organ. The clinical manifestations and prognosis vary widely depending on the specific type of the affected protein. Immunoglobulin light-chain (AL) amyloidosis is the most common form of systemic amyloidosis, characterized by deposition of a misfolded monoclonal light-chain that is secreted from a plasma cell clone. Demonstrating amyloid deposits in a tissue biopsy stained with Congo red is mandatory for the diagnosis. Novel agents (proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, venetoclax) and autologous stem cell transplantation, used for eliminating the underlying plasma cell clone, have improved the outcome for low- and intermediate-risk patients, but the prognosis for high-risk patients is still grave. Randomized studies evaluating antibodies that target the amyloid deposits (PRONTO, VITAL) were recently stopped due to futility and currently there is an intensive search for novel treatment approaches to AL amyloidosis. Early diagnosis is of paramount importance for effective treatment and prognosis, due to the progressive nature of this disease.