Light-chain amyloidosis: SCT, novel agents and beyond

摘要

Light-chain amyloidosis is a plasma cell dyscrasia characterized by the production of fibrillar proteins comprised of monoclonal light chains, which deposit in tissues causing multiorgan dysfunction and death. The diagnosis is challenging and requires a biopsy and often specialized testing to confirm the subtype of systemic disease. The goal of treatment is eradication of the monoclonal plasma cell population and suppression of the pathologic light chains, which improve organ function and extend survival. Standard treatment approaches have included high-dose melphalan followed by autologous hematopoietic SCT or oral melphalan with dexamethasone. The use of novel agents (thalidomide, lenalidomide and bortezomib) alone and in combination with steroids and alkylating agents has shown efficacy and continues to be explored. A risk-adapted approach to SCT followed by novel agents as consolidation, reduces treatment-related mortality with promising activity. Immunotherapy targeting pathologic plasma cells and amyloid fibrils is being developed and could potentially eliminate visceral amyloid deposits. Improved understanding of the biology that renders light-chains amyloidogenic and a commitment to refer patients to specialized centers conducting well-designed clinical trials is essential to improve patient outcomes.