Hematological Treatments and Disease Modifying Therapies in AL Cardiac Amyloidosis

Light-chain AL amyloidosis (AL) is a rare plasma cell disorder (PCD) characterized by multi-organ damage due to misfolded immunoglobulin light chains (LC) secreted by clonal abnormal plasma cells (PC). In the last decade significant progress has been made in the care of this disease, with the use of efficacious novel agents that enable the eradication of the abnormal PC, leading to the cessation of toxic light chain secretion and eventually improvement in organ function. Treatment of AL has traditionally followed that of the much more common PCD multiple myeloma (MM), utilizing a combination of PC-targeted agents, while therapies directly targeting the amyloid fibrils formation and accumulation are only investigational. Discussed here are general concepts of AL treatment approaches, as well as revision of the data on approved therapies and investigational approaches. Alkylating agents and steroids are still utilized, but now accompanied in frontline therapy by bortezomib; a proteosome inhibitor, and an anti-CD38 antibody. Autologous stem-cell transplant is a valuable option for eligible patients. Though prospective data is scarce, other anti-PC agents like immune modulators and more recently venetoclax (utilized for patients with the translocation 11:14) and belantamab mafodotin are optional for relapsed/refractory disease. Following the pronounced advances in therapy for MM, immunotherapies such as bispecific antibodies and chimeric antigen receptor T-cell (CART) may become a valuable option for AL amyloidosis. Finally, antibodies targeting the amyloidogenic LC and promoting its clearance are under extensive investigation. In conclusion, AL patients may currently be treated by a variety of effective therapies. The landscape of this disease is rapidly changing, and it is likely that in the next few years further progress will be made in the care of these patients.