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ABSTRACT Systemic immunoglobulin light chain amyloidosis is a protein misfolding disease caused by the conversion of immunoglobulin light chains from their soluble functional states into

highly organized amyloid fibrillar aggregates that lead to organ dysfunction. The disease is progressive and, accordingly, early diagnosis is vital to prevent irreversible organ damage, of

which cardiac damage and renal damage predominate. The development of novel sensitive biomarkers and imaging technologies for the detection and quantification of organ involvement and damage

is facilitating earlier diagnosis and improved evaluation of the efficacy of new and existing therapies. Treatment is guided by risk assessment, which is based on levels of cardiac

biomarkers; close monitoring of clonal and organ responses guides duration of therapy and changes in regimen. Several new classes of drugs, such as proteasome inhibitors and immunomodulatory

drugs, along with high-dose chemotherapy and autologous haematopoietic stem cell transplantation, have led to rapid and deep suppression of amyloid light chain production in the majority of

patients. However, effective therapies for patients with advanced cardiac involvement are an unmet need. Passive immunotherapies targeting clonal plasma cells and directly accelerating

removal of amyloid deposits promise to further improve the overall outlook of this increasingly treatable disease. Access through your institution Buy or subscribe This is a preview of

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ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS IMMUNOGLOBULIN LIGHT CHAIN AMYLOIDOSIS

DIAGNOSIS AND TREATMENT ALGORITHM 2021 Article Open access 15 May 2021 COMPREHENSIVE REVIEW OF AL AMYLOIDOSIS: SOME PRACTICAL RECOMMENDATIONS Article Open access 18 May 2021 THE MANAGEMENT

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amyloidosis. _Blood_ 125, 3281–3286 (2015). CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS G.M. and G.P. are supported in part by grants from ‘Associazione Italiana per la

Ricerca sul Cancro–Special Program Molecular Clinical Oncology 5 per mille n. 9965’, from CARIPLO ‘Structure-function relation of amyloid: understanding the molecular bases of protein

misfolding diseases to design new treatments n. 2013–0964’ and from CARIPLO ‘Molecular mechanisms of immunoglobulin toxicity in age-related plasma cell dyscrasias n. 2015–0591’. G.P. is

supported in part by the Bart Barlogie Young Investigator Award from the International Myeloma Society. REVIEWER INFORMATION _Nature Reviews Disease Primers_ thanks J. Blade, R. Comenzo, B.

Hazenberg, S. Ikeda, A. Jaccard, R. Linke and the other, anonymous referee(s) for their contribution to the peer review of this work. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS *

Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy Giampaolo Merlini & Giovanni Palladini * Department of Molecular Medicine, University of

Pavia, Pavia, Italy Giampaolo Merlini & Giovanni Palladini * Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA Angela Dispenzieri & Morie A.

Gertz * Section of Hematology-Oncology and Amyloidosis Center, Boston University School of Medicine, Boston, MA, USA Vaishali Sanchorawala * Department of Internal Medicine V (Haematology,

Oncology and Rheumatology), Amyloidosis Center, University Hospital Heidelberg, Heidelberg, Germany Stefan O. Schönland * National Amyloidosis Centre, University College London (Royal Free

Campus), London, UK Philip N. Hawkins Authors * Giampaolo Merlini View author publications You can also search for this author inPubMed Google Scholar * Angela Dispenzieri View author

publications You can also search for this author inPubMed Google Scholar * Vaishali Sanchorawala View author publications You can also search for this author inPubMed Google Scholar * Stefan

O. Schönland View author publications You can also search for this author inPubMed Google Scholar * Giovanni Palladini View author publications You can also search for this author inPubMed 

Google Scholar * Philip N. Hawkins View author publications You can also search for this author inPubMed Google Scholar * Morie A. Gertz View author publications You can also search for this

author inPubMed Google Scholar CONTRIBUTIONS Introduction (G.M.); Epidemiology (A.D. and M.A.G.); Mechanisms/pathophysiology (G.M.); Diagnosis, screening and prevention (A.D., G.P., P.N.H.

and M.A.G.); Management (G.M., A.D., V.S., S.O.S., G.P., P.N.H. and M.A.G.); Quality of life (V.S.); Outlook (G.M. and P.N.H.); Overview of the Primer (G.M.). CORRESPONDING AUTHOR

Correspondence to Giampaolo Merlini. ETHICS DECLARATIONS COMPETING INTERESTS G.M. is on the advisory board for Caelum, Janssen and Pfizer and has received travel support from Janssen and

Prothena. A.D. receives research support from Alnylam, Celgene, GlaxoSmithKline, Pfizer and Takeda and has received research support from Prothena. V.S. sits on the advisory boards of

Caelum, Janssen, receives research support from Celgene, Janssen and Takeda and has received research support from Prothena. S.O.S. has received honoraria and research support from Prothena

and receives honoraria from Janssen, travel support from Jazz and Takeda and research support from Janssen and Sanofi. G.P. sits on the advisory board of Janssen, has received honoraria from

Prothena and receives honoraria from Sebia and travel support from Celgene. P.N.H. receives honoraria from Alnylam and GlaxoSmithKline and is a director and stockholder of Pentraxin

Therapeutics. M.A.G. receives honoraria from Abbvie, Alnylam, Amgen, Annexon, Appellis, Celgene, Ionis, Janssen, Johnson and Johnson, Medscape, Physicians Education Resource, Prothena,

Research to Practice, Spectrum and Teva and receives research support from Spectrum. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional

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Merlini, G., Dispenzieri, A., Sanchorawala, V. _et al._ Systemic immunoglobulin light chain amyloidosis. _Nat Rev Dis Primers_ 4, 38 (2018). https://doi.org/10.1038/s41572-018-0034-3

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