Advancements and future trends of immunotherapy in light-chain amyloidosis. (March 2023) - Mahadevia, Himil
Abstract: Light-chain (AL) amyloidosis is a type of plasma cell neoplasm with abnormal monoclonal immunoglobulin light-chain production and their subsequent deposition in tissues causing end-organ damage. In addition to existing treatments including autologous stem cell transplantation, there is a need for other approaches for eradicating abnormal plasma cells and amyloid tissue deposits. Treatment strategies of AL amyloidosis are mostly based on medications that are effective in multiple myeloma due to similar cell of origin. Daratumumab along with proteasome inhibitors and corticosteroids has become standard of care for AL amyloidosis. Another appealing approach is disassembling amyloid deposits with hope to potentially reverse the damage done by the disease. This was met with promising results for CAEL-101 and birtamimab. Although still in early stages, novel treatment options in pipeline, including antibody-drug conjugates, bispecific T-cell engagers, and chimeric antigen receptor T cell therapy may diversify the treatment armamentarium of AL amyloidosis in the future. Highlights: Novel antibodies targeted at plasma cells (anti-CD38, anti-SLAMF7) have shown promise in refractory AL amyloidosis. Antibodies designed to clear amyloid deposits in tissue may enable us to more effectively reverse end organ damage. CAR-T therapy and ADCs have shown some early success in AL amyloidosis and trials may be conducted in the future. Combining immunotherapies that target different antigens on plasma cells may reduce the incidence of refractoriness. Combining immunotherapies targeted at plasma cells and amyloid deposits may lead to superior organ response rates.