How to manage primary amyloidosis

Abstract

Immunoglobulin light chain amyloidosis is a protein deposition disorder where the precursor protein represents a monoclonal immunoglobulin light or heavy chain. Deposition in viscera results in restrictive cardiomyopathy, nephrotic range proteinuria, demyelinating peripheral neuropathy, hepatomegaly and malabsorption syndrome. Diagnosis requires biopsy with Congo red staining. Invasive biopsies are not required generally. It is essential that after a histologic diagnosis is obtained, the tissue is validated to have an immunoglobulin light chain composition so patients are spared unnecessary chemotherapy. The disease prognosis and patient monitoring are linked to serialized measurement of cardiac biomarkers and immunoglobulin-free light chains. Most patients require cytotoxic chemotherapy. For some patients, this therapy involves stem cell collection and myeloablative chemotherapy; for others, chemotherapy includes an alkylator and a corticosteroid; and for some, it involves addition of a novel agent in the form of an immunomodulatory drug or a proteasome inhibitor. Delays in diagnosis continue to be an obstacle to initiating effective therapy. Early mortality rates remain high. Effective chemotherapy can result in reversal of organ dysfunction and recovery. Reductions in light chain production translate to improved survival.

Melphalan and dexamethasone with or without bortezomib in newly diagnosed AL amyloidosis: a matched case–control study on 174 patients

“…Treatment approaches are derived from multiple myeloma and are adapted to the fragile amyloid patients, and novel agents are finding their place in the therapeutic armamentarium for AL amyloidosis. 9,10 Bortezomib is now a mainstay in the treatment of multiple myeloma. 11 Treatment approaches based on proteasome inhibition are expected to be highly efficacious in AL amyloidosis, because amyloidogenic plasma cells rely on proteasome activity to deal with the proteotoxic stress caused by the misfolded light chain.…”

Best use of cardiac biomarkers in patients with AL amyloidosis and renal failure

“…Moreover, NT-proBNP is a reliable and useful marker of cardiac response and progression after chemotherapy [4,5]. Based on these findings, measurement of NT-proBNP is now viewed as a useful tool in the workup of patients with AL amyloidosis at diagnosis and during treatment [6,7]. However, the clearance and, consequently, the serum concentration of natriuretic peptides are influenced by glomerular filtration [8,9].…”

Clinical features and treatment outcome of primary systemic light‐chain amyloidosis in Korea: Results of multicenter analysis

“…Overall prognosis of AL amyloidosis is worse than multiple myeloma even though bone marrow plasma cell volume and the extent of monoclonal proteins are small because the involved organ impairment accounts for the prognosis of AL amyloidosis. Thus, survival of patients with AL amyloidosis is dependent on the number of affected organ and the severity of organ dysfunction, especially involvement of heart and response to chemotherapy [2]. Unfortunately, it is still unclear regarding the mechanism of the formation of amyloid fibril and organ involvement.…”