Recent developments in systemic light-chain amyloidosis prognosis and treatment.

Abstract

Systemic light-chain (AL) amyloidosis is a rare clonal plasma cell disorder characterized by the production of abnormal immunoglobulin free light-chains that misfold into amyloid fibrils and deposit in the extracellular matrix of tissues. Despite being a multisystemic disease process, the presence and severity of cardiac involvement remains the main determinant of prognosis. Improved understanding of the underlying pathophysiology has resulted in transformative changes in both diagnostics and treatment. Improvements in multimodality cardiac imaging have enabled accurate diagnosis, facilitated rapid initiation of treatment and allowed the direct visualization changes in the myocardial substrate in response to chemotherapy. Significant progress has also been made through leveraging treatments that directly target the underlying abnormal plasma cell clone responsible the production of the amyloidogenic immunoglobulin free light-chains. Current treatment options successfully target amyloid production, but novel anti-amyloid therapies seek to target amyloid fibrils that have already deposited in the organs and facilitate their removal through an immune-mediated degradation process are at advanced stages of development. These treatments have the potential to induce disease regression by depleting amyloid deposits and if successful will represent a significant step forward in the treatment of systemic AL amyloidosis, especially for patients with advanced cardiac disease.