Treatment of AL amyloidosis

AL amyloidosis is caused by the conversion of monoclonal immunoglobulin light chains into amyloid fibrillar aggregates that deposit in tissue and lead to organ dysfunction. Diagnosis is histological and relies primarily on non-invasive biopsies, showing Congo red-positive amorphous deposits containing immunoglobulin light chains, most commonly of lambda isotype. The clinical presentation is extremely polymorphous, due to the large number of organs that can be affected by the disease. The kidneys and the heart are most frequently involved organs, in about two thirds of patients each, responsible for nephrotic syndrome and restrictive cardiomyopathy. Treatment is based on chemotherapy aimed at eliminating the medullary clone producing the pathogenic monoclonal light chains. It is guided by risk assessment, based on the serum levels of cardiac biomarkers. Its effectiveness must be regularly assessed by the serum free light chain assay. Current reference regimens combine an alkylating agent, with high doses of dexamethasone and most often a proteasome inhibitor. They are effective in the majority of patients. The overall prognosis depends on the importance of the initial severity of organ involvement, particularly the heart, and is strongly influenced by the haematological response. The treatment must be rapidly modified in non-responders, especially in those with severe cardiac disease, with the introduction of immunomodulatory drugs and antibodies targeting plasma cells. However, effective therapies for patients with the more severe amyloid cardiopathy are an unmet need. Strategies directly accelerating the removal of amyloid deposits, despite disappointing preliminary results, could further improve the prognosis of this disease.