AL amyloidosis

Amyloidosis is a rare group of disorders with protean manifestations characterized by tissue deposition of misfolded protein. This causes progressive accumulation of amyloid deposits and disruption of organ function. Among patients with systemic amyloidosis, AL-type protein is the most common. This article focuses on AL amyloidosis, formerly known as primary amyloidosis, which usually affects the kidneys, heart, liver and peripheral nervous system. Diagnosis is rarely made until symptoms are referable to a particular organ. Untreated, it is progressive and fatal. Prognosis is determined by the extent of cardiac involvement. The three-step approach to diagnosis and investigation involves confirmation of amyloid and type, assessing the extent of organ involvement and confirmation of an underlying plasma cell dyscrasia/lymphoma. Treatment aims to reduce production of amyloidogenic light chains and stop progressive organ function deterioration. New drug classes such as proteasome inhibitors, immunomodulatory agents and anti-CD38 monoclonal antibodies have shown promise in reducing the light-chain burden, halting amyloid production and subsequently improving organ response and survival. Autologous stem cell transplantation has improved survival rates but is available only to a limited patient cohort. Bispecific antibodies, chimeric antigen receptor T cell therapies and agents directly removing amyloid fibrils in development show encouraging results in selected group of patients.