Bad players in AL amyloidosis in the current era of treatment

ABSTRACT

Introduction

Systemic AL amyloidosis (ALA) is a clonal plasma cell (PC) disease characterized by deposition of amyloid fibrils in different organs and tissues. Traditionally, the prognosis of ALA is poor and is primarily defined by cardiac involvement. The modern prognostic models are based on cardiac markers and free light chain difference (dFLC). Cardiac biomarkers have low specificity and are dependent on renal function, volume status, and cardiac diseases other than ALA. New therapies significantly improved the prognosis of the disease. The advancements in technologies – cardiac echocardiography (ECHO) and cardiac MRI (CMR), as well as new biological markers, relying on cardiac injury, inflammation, endothelial damage, and clonal and non-clonal PC markers are promising.

Areas covered

An update on the prognostic significance of cardiac ALA, number of involved organs, response to treatment, including minimal residual disease (MRD), ECHO, MRI, and new biological markers will be discussed. The literature search was done in PubMed and Google Scholar, and the most recent and relevant data are included.

Expert opinion

Prospective multicenter trials, evaluating multiple clinical and laboratory parameters, should be done to improve the risk assessment models in ALA in the modern era of therapy.

KEYWORDS:

• AL amyloidosis
• systemic amyloidosis
• prognosis
• biological markers
• cardiac amyloidosis
• immunoglobulin free light chains
• BNP
• troponin

Article highlights

• Cardiac involvement is the major prognostic factor in ALA, and serum biological markers of cardiac injury – NT-proBNP and troponin – are most important in risk assessment but are not specific and can fluctuate depending on renal function, volume status, treatment based on immunomodulatory drugs (IMIDs) and cardiac damage due to other causes.

• 6-MWT is easy to perform and shows excellent prognostic performance in ALA

• Early and deep hematologic response improve outcomes of ALA even when advanced cardiac involvement is present.

• New biological markers are promising and are currently under investigation in ALA.

Acknowledgments

The figures for this manuscript were prepared with Biorender.com

Declaration of interest

N Kreiniz has received payment for lectures and presentations from Roche, Novartis, and Neopharm and support for attending meetings and/or travel from Pfizer and Takeda. M Gertz has received funding and personal fees from Ionis/Akcea, honorarium from Alnylam, personal fees from Prothena, Sanofi, Janssen, Aptitude Healthgrants, Ashfiel, Juno, the Physicians Education Resource, personal fees for Data Safety Monitoring board from AbbVie, fees from Johnson & Johnson, and Celgene, personal fees from Research to Practice, personal fees for meetings from Sorrento, and the development of educational materials for i3Health. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.