Light-chain amyloidosis (AL) “once upon a time there was an incurable disease”: progresses from almost no cure to a personalized therapy.

Abstract

Survival of patients with a light chain (AL) amyloidosis has gradually but constantly improved in the last 30 years. While we used to have only very few molecules available for treating the disease, we now have a great choice of drugs that can target the disease at different levels. The present therapeutic approach, derived from the current experience with multiple myeloma, is risk-adapted according to cardiac biomarkers staging at diagnosis. Patients are classified into low, intermediate, or high-grade risk groups according to their values of the cardiac biomarkers NT-proBNP and Troponin I/T: both normal (low risk), one out of two abnormal (intermediate risk), or both abnormal (high risk). Only patients with a low-grade risk (accounting for less than 20%) are allowed to undergo autologous stem cell transplantation (ASCT). Intermediate and high-risk patients are offered standard therapies, such as alkylators (melphalan or cyclophosphamide) plus dexamethasone, with or without proteasome inhibitors. Immunomodulatory imide drugs (IMiDs) have been used mostly for rescue treatment. Organ response is the final aim of the therapy, but it can occur only when a complete or very good hematological response is obtained. Hematological and organ response assessment help monitoring the disease and allow prompt identification of refractory/relapsed patients that need to undergo rescue therapy. New agents are currently under study and will soon be available for clinical use in combination with traditional anti-plasma cell chemotherapy.