Systemic AL Amyloidosis and Precision Medicine

Abstract

In amyloid light-chain (AL) amyloidosis, a small plasma-cell clone, or less frequently a mature B-cell clone, produces toxic monoclonal light chains that can be deposited in the tissues in the form of amyloid fibrils, which can affect the function of potentially multiple organs, including the heart and kidney. The mechanisms behind this organ function impairment are different from plasma-cell myeloma, as are the diagnostic work-up and the treatment strategies. Early pre-symptomatic diagnosis of AL amyloidosis is possible, and it is indeed crucial for effective therapy and the preservation of patients' quality of life. This is however challenging in the light of a lack of specific clinical symptoms or signs. In the case of suspicious clinical signs, along with the presence of monoclonal gammopathy and elevated validated biomarkers of organ involvement, further diagnostic workup should be initiated to confirm or exclude AL amyloidosis. Tissue typing of amyloid is also mandatory for the diagnosis of AL amyloidosis. Risk-stratification is essential to guide the therapeutic approach, which has to be individualized and take patient preferences into account. The aim of the therapy is rapid suppression of the production of light chains, to restore organ function, especially cardiac function. The severity of heart involvement and the burden of the pathological light chains are the main prognostic determinants in AL amyloidosis. This review discusses the diagnostic algorithms in suspected amyloidosis, the need for typing of the amyloid for prognostic and therapeutic reasons, and the recent developments in the risk-adapted treatment of AL amyloidosis. We further focus on anti-plasma-cell drugs and autologous stem-cell transplantation, as the tools for hematologic and organ response assessment.

Swiss Amyloidosis Network (SAN): Objectives and Challenges

“…However, establishing the diagnosis of amyloidosis can be challenging. [3][4][5][6] Systemic amyloidosis is a group of rare diseases. Understandably, many healthcare providers are not familiar with the clinical symptoms, diagnostic criteria, and treatment options of these diseases.…”

“…In high-risk patients, there is still no established standard therapy, and the treatment has to be individualized based on comorbidities and toxicity. 4,5 Swiss Amyloidosis Network (SAN): Objectives and Challenges…”