In the plenary session on Sunday Professor Giampaolo Merlini (University of Pavia, Italy) presented an overview of recent developments in the diagnosis and outcome of AL amyloidosis.
In this most common type of amyloidosis, mutations lead to misfolding and destabilization of the immunoglobulin light chain, which is then broken down into oligomers that form amyloid fibrils. This results in amyloid deposits, specifically in the heart, kidney and liver. Approximately 10-15% of multiple myeloma (MM) patients develop AL amyloidosis. Patients with symptomatic heart involvement have a poor median survival of 15 months.
“Early diagnosis is of vital importance”, Merlini said. This can be achieved by combining biomarkers (e.g. sFLC, NT-proBNP) with imaging techniques (e.g. echocardiography, cardiac MRI, 18F-florbetapir PET/CT). Biomarkers can also predict outcomes of these patients, and staging systems have been developed that can identify patients with advanced cardiac or renal dysfunction. Merlini described an algorithm for the diagnosis of systemic amyloidosis, based on the combined use of biomarkers and imaging. Characterization of the amyloidogenic clone can predict outcome and inform treatment decisions.
Therapy aimed at decreasing the amyloid precursor and removal of amyloid deposits can improve organ (cardiac) function, and has markedly extended survival in recent years. In fit patients (~20%), stem cell transplantation is extremely effective. Most patients (~60%) receive bortezomib-based regimens. Merlini discussed several novel agents and treatments that are in development. Combinations of targeted agents may further improve outcome. “This opens new possibilities, but at the same time raises concerns about sustainability and access to drugs.”