New concepts in the treatment and diagnosis of amyloidosis

ABSTRACT

Introduction: The most common form of systemic amyloidosis in Western countries is light chain amyloidosis. It is characterized by the deposition of a misfolded light chain in target organs. This amyloid precursor is produced by a usually small but dangerous B-cell clone.

Areas covered: This review examines the diagnostic workup of this disease and current knowledge of biomarker-based staging systems. In addition, a risk-adapted treatment approach is presented, as well as an overview of the new treatment strategies.

Expert commentary: The cornerstone of treatment is rapid and effective chemotherapy targeting the underlying plasma cell clone. In the near future, this will probably be associated with novel approaches targeting other steps of the amyloid cascade that result in amyloid deposits. Currently available effective treatments can alter its natural history if an early diagnosis is made. The availability of novel, more powerful drugs, and identification of the cellular mechanisms of organ damage and of the characteristics of the amyloidogenic plasma-cell clone all give grounds to hope that a dramatic improvement in the treatment of this disease will be seen in the near future.

KEYWORDS:

• Amyloidosis
• response
• diagnosis
• prognosis
• therapy

Acknowledgments

The authors thank Anne Freckleton for English editing.

Declaration of interest

One author is a consultant for Millennium Pharmaceuticals, Pfizer, Janssen, Prothena, and IONIS. One author has received honoraria from Jannsen-Cilag and Prothena, and travel support from Prothena and Celgene. 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.

Additional information

Funding

This work was supported in part by ‘Associazione Italiana per la Ricerca sul Cancro–Special Program Molecular Clinical Oncology 5 per mille’ (grant 9965), CARIPLO ‘Structure-function relation of amyloid: understanding the molecular bases of protein misfolding diseases to design new treatments’ (grant 2013-0964), and the Italian Ministry of Health target project (grant RF-2013-02355259). GP is supported in part by the Bart Barlogie Young Investigator Award from the International Myeloma Society (IMS).