Use of novel therapies in the treatment of light chain amyloidosis.

Immunoglobulin light-chain (AL) amyloidosis is a rare life-threatening disease caused by light chains that are toxic to vital organs such as the heart, kidneys, liver and peripheral nervous system, and that misfold and assemble as amyloid fibrils and deposit both in affected organs and systemically in the vasculature and other tissues. Patients afflicted by this disease have B-cell disorders, almost always related to clonal plasma cells in the bone marrow, the burden of which can range from small clones involving 5% or less of marrow cells to frank multiple myeloma. The goal of therapy is to eliminate the clonal plasma cells producing these toxic light chains to halt and possibly reverse symptomatic organ damage. While autologous stem cell transplantation can be a very effective treatment modality in AL, it has a limited role due to the frailty of this particular population. Conservative treatment in the form of chemotherapy has become the backbone of therapy. Bortezomib combined with alkylators has proven quite successful in inducing hematologic responses. However, despite these advances, tolerability and resistance continue to be an ongoing issue. Novel anti-plasma cell therapies such as ixazomib, carfilzomib, lenalidomide and pomalidomide are actively being combined and evaluated in clinical trials for efficacy and toxicity in this challenging patient population. Other approaches, such as monoclonal antibodies targeting surface proteins and amyloid deposits, are being tested and combined with novel agents. In this review, we will provide an overview of the clinical trials that have led to current treatment algorithms and will also discuss monoclonal antibodies currently under investigation and in various stages of clinical development.