Nonchemotherapy Treatment of Immunoglobulin Light Chain Amyloidosis

Abstract

Immunoglobulin light chain amyloidosis (AL amyloidosis) is a rare, life-threatening disease characterized by the deposition of misfolded proteins in vital organs such as the heart, the lungs, the kidneys, the peripheral nervous system, and the gastrointestinal tract. This causes a direct toxic effect, eventually leading to organ failure. The underlying B-cell lymphoproliferative disorder is almost always a clonal plasma cell disorder, most often a small plasma cell clone of <10%. Current therapy is directed toward elimination of the plasma cell clone with the goal of preventing further organ damage and reversal of the existing organ damage. Autologous stem cell transplantation has been shown to be a very effective treatment in patients with AL amyloidosis, although it cannot be widely applied as patients are often frail at presentation, making them ineligible for transplantation. Treatment with cyclophosphamide, bortezomib, and dexamethasone has emerged as the standard of care for the treatment of AL amyloidosis. Novel anti-plasma cell therapies, such as second generation proteasome inhibitors, immunomodulators, monoclonal antibodies targeting a surface protein on the plasma cell (daratumumab, elotuzumab), and the small molecular inhibitor venetoclax, have continued to emerge and are being evaluated in combination with the standard of care. However, there is still a need for therapies that directly target the amyloid fibrils and reverse organ damage. In this review, we will discuss current and emerging nonchemotherapy treatments of AL amyloidosis, including antifibril directed therapies under current investigation.