Guidelines Summary

In 2015, Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) released consensus guidelines for the treatment of immunoglobulin light chain amyloidosis. Key recommendations include the following^[39]:

Initiate treatment immediately in virtually all patients with systemic AL amyloidosis.
Consider high-dose chemotherapy with autologous stem cell transplant (ASCT) in selected patients based on troponin level, blood pressure, kidney function, and physiologic age.
Dose-attenuated conditioning chemotherapy with ASCT is not recommended outside of a clinical trial.
Induction therapy before ASCT is recommended for patients with 10% or greater bone marrow plasmacytosis.
ASCT for patients undergoing hemodialysis is feasible, especially if kidney transplantation is being considered.
For patients with underlying lymphoproliferative disease or IgM monoclonal protein, ASCT is a reasonable option.
For patients ineligible for ASCT, standard-dose melphalan and dexamethasone is a valuable first-line option and the combination of thalidomide, cyclophosphamide, and dexamethasone is potentially beneficial as first-line therapy.
Cyclophosphamide, bortezomib, and dexamethasone or bortezomib, melphalan, and dexamethasone can be used in patients with newly diagnosed or relapsed disease, but neither regimen has been systematically studied.

Medication

Hamidi Asl K, Liepnieks JJ, Nakamura M, Benson MD. Organ-specific (localized) synthesis of Ig light chain amyloid. J Immunol. 1999 May 1. 162 (9):5556-60. [QxMD MEDLINE Link]. [Full Text].
Kyle RA, Larson DR, Kurtin PJ, Kumar S, Cerhan JR, Therneau TM, et al. Incidence of AL Amyloidosis in Olmsted County, Minnesota, 1990 through 2015. Mayo Clin Proc. 2019 Mar. 94 (3):465-471. [QxMD MEDLINE Link].
Nienhuis HL, Bijzet J, Hazenberg BP. The Prevalence and Management of Systemic Amyloidosis in Western Countries. Kidney Dis (Basel). 2016 Apr. 2 (1):10-9. [QxMD MEDLINE Link]. [Full Text].
Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol. 1995 Jan. 32(1):45-59. [QxMD MEDLINE Link].
Apridonidze T, Steingart RM, Comenzo RL, Hoffman J, Goldsmith Y, Bella JN, et al. Clinical and Echocardiographic Correlates of Elevated Troponin in Amyloid Light-Chain Cardiac Amyloidosis. Am J Cardiol. 2012 Jul 5. [QxMD MEDLINE Link].
Nelson LM, Gustafsson F, Gimsing P. Characteristics and Long-Term Outcome of Patients with Systemic Immunoglobulin Light-Chain Amyloidosis. Acta Haematol. 2014 Dec 16. 133(4):336-346. [QxMD MEDLINE Link].
Warsame R, Bang SM, Kumar SK, Gertz MA, Lacy MQ, Buadi F, et al. Outcomes and treatments of patients with immunoglobulin light chain amyloidosis who progress or relapse postautologous stem cell transplant. Eur J Haematol. 2014 Jun. 92(6):485-90. [QxMD MEDLINE Link].
Muchtar E, Gertz MA, Kumar SK, Lacy MQ, Dingli D, Buadi FK, et al. Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death. Blood. 2017 Apr 13. 129 (15):2111-2119. [QxMD MEDLINE Link].
Leibovitch I, Selva D, Goldberg RA, et al. Periocular and orbital amyloidosis: clinical characteristics, management, and outcome. Ophthalmology. 2006 Sep. 113(9):1657-64. [QxMD MEDLINE Link].
Cross TJ, Wendon JA, Quaglia A, et al. Myeloma associated amyloidosis presenting as subacute liver failure. Postgrad Med J. 2006 Jul. 82(969):e13. [QxMD MEDLINE Link].
Kumar S, Dispenzieri A, Katzmann JA, et al. Serum immunoglobulin free light-chain measurement in primary amyloidosis: prognostic value and correlations with clinical features. Blood. 2010 Dec 9. 116(24):5126-9. [QxMD MEDLINE Link]. [Full Text].
Dispenzieri A, Lacy MQ, Katzmann JA, et al. Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. Blood. 2006 Apr 15. 107(8):3378-83. [QxMD MEDLINE Link]. [Full Text].
Porrata LF, Gertz MA, Litzow MR, et al. Early lymphocyte recovery predicts superior survival after autologous hematopoietic stem cell transplantation for patients with primary systemic amyloidosis. Clin Cancer Res. 2005 Feb 1. 11(3):1210-8. [QxMD MEDLINE Link]. [Full Text].
Paiva B, Vídriales MB, Pérez JJ, López-Berges MC, García-Sanz R, Ocio EM, et al. The clinical utility and prognostic value of multiparameter flow cytometry immunophenotyping in light-chain amyloidosis. Blood. 2011 Mar 31. 117(13):3613-6. [QxMD MEDLINE Link].
Knight DS, Zumbo G, Barcella W, Steeden JA, Muthurangu V, Martinez-Naharro A, et al. Cardiac Structural and Functional Consequences of Amyloid Deposition by Cardiac Magnetic Resonance and Echocardiography and Their Prognostic Roles. JACC Cardiovasc Imaging. 2019 May. 12 (5):823-833. [QxMD MEDLINE Link].
Tuzovic M, Yang EH, Baas AS, Depasquale EC, Deng MC, Cruz D, et al. Cardiac Amyloidosis: Diagnosis and Treatment Strategies. Curr Oncol Rep. 2017 Jul. 19 (7):46. [QxMD MEDLINE Link].
Agha AM, Parwani P, Guha A, Durand JB, Iliescu CA, Hassan S, et al. Role of cardiovascular imaging for the diagnosis and prognosis of cardiac amyloidosis. Open Heart. 2018. 5 (2):e000881. [QxMD MEDLINE Link]. [Full Text].
Chopra A. ¹²⁵I-Labeled single-chain monoclonal antibody, NS4F5, that targets the GlcNS6S-IdoA2S motif of heparan sulfate proteoglycans for the in vivo imaging of peripheral amyloidosis. 2004. [QxMD MEDLINE Link].
Wall JS, Richey T, Williams A, Stuckey A, Osborne D, Martin E, et al. Comparative analysis of peptide p5 and serum amyloid P component for imaging AA amyloid in mice using dual-isotope SPECT. Mol Imaging Biol. 2012 Aug. 14(4):402-7. [QxMD MEDLINE Link]. [Full Text].
Wall JS, Kennel SJ, Stuckey AC, Long MJ, Townsend DW, Smith GT. Radioimmunodetection of amyloid deposits in patients with AL amyloidosis. Blood. 2010 Sep 30. 116(13):2241-4. [QxMD MEDLINE Link].
Pan WH, Li NP. Clinical pathological feature of early tongue amyloidosis. Chin Med Sci J. 2006 Jun. 21(2):104-6. [QxMD MEDLINE Link].
Zumbo G, Sadeghi-Alavijeh O, Hawkins PN, Fontana M. New and developing therapies for AL amyloidosis. Expert Opin Pharmacother. 2017 Feb. 18 (2):139-149. [QxMD MEDLINE Link].
Kyle RA, Gertz MA, Greipp PR, et al. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone, and colchicine. N Engl J Med. 1997 Apr 24. 336(17):1202-7. [QxMD MEDLINE Link]. [Full Text].
Skinner M, Anderson J, Simms R, et al. Treatment of 100 patients with primary amyloidosis: a randomized trial of melphalan, prednisone, and colchicine versus colchicine only. Am J Med. 1996 Mar. 100(3):290-8. [QxMD MEDLINE Link].
Gertz MA, Lacy MQ, Lust JA, et al. Prospective randomized trial of melphalan and prednisone versus vincristine, carmustine, melphalan, cyclophosphamide, and prednisone in the treatment of primary systemic amyloidosis. J Clin Oncol. 1999 Jan. 17(1):262-7. [QxMD MEDLINE Link]. [Full Text].
Anderson K, Richardson P, Chanan-Khan A, et al. Single-agent bortezomib in previously untreated multiple myeloma (MM): results of a phase II multicenter study [abstract 7504]. J Clin Oncol. 2006. 24:423s.
Dispenzieri A, Zhang L, Fonseca R, et al. Single agent bortezomib is associated with a high response rate in patients with high risk myeloma. A phase II study from the Eastern Cooperative Oncology Group (E2A02) [abstract 3527]. Blood. 2006. 108(11):1006s. [Full Text].
Mateos MV, Richardson PG, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, et al. Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. J Clin Oncol. 2010 May 1. 28(13):2259-66. [QxMD MEDLINE Link].
Harousseau JL, Palumbo A, Richardson PG, Schlag R, Dimopoulos MA, Shpilberg O, et al. Superior outcomes associated with complete response in newly diagnosed multiple myeloma patients treated with nonintensive therapy: analysis of the phase 3 VISTA study of bortezomib plus melphalan-prednisone versus melphalan-prednisone. Blood. 2010 Nov 11. 116(19):3743-50. [QxMD MEDLINE Link].
Harousseau JL, Attal M, Leleu X, et al. Bortezomib plus dexamethasone as induction treatment prior to autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: results of an IFM phase II study. Haematologica. 2006 Nov. 91(11):1498-505. [QxMD MEDLINE Link]. [Full Text].
Dou QP, Zonder JA. Overview of proteasome inhibitor-based anti-cancer therapies: perspective on bortezomib and second generation proteasome inhibitors versus future generation inhibitors of ubiquitin-proteasome system. Curr Cancer Drug Targets. 2014. 14 (6):517-36. [QxMD MEDLINE Link]. [Full Text].
Lenalidomide (Revlimid). U.S. Food & Drug Administration. Available at https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm542791.htm. February 22, 2107; Accessed: November 30, 2019.
San Miguel J, Weisel K, Moreau P, Lacy M, Song K, Delforge M, et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Oct. 14(11):1055-66. [QxMD MEDLINE Link].
Richardson PG1, Siegel DS, Vij R, Hofmeister CC, Baz R, Jagannath S, et al. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood. 2014. 123:1826-32. [Full Text].
US Food & Drug Administration. FDA grants accelerated approval to Darzalex Faspro for newly diagnosed light chain amyloidosis. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-darzalex-faspro-newly-diagnosed-light-chain-amyloidosis. January 15, 2021; Accessed: June 26, 2022.
Kastritis E, et al; ANDROMEDA Trial Investigators. Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis. N Engl J Med. 2021 Jul 1. 385 (1):46-58. [QxMD MEDLINE Link].
Gianni L, Bellotti V, Gianni AM, Merlini G. New drug therapy of amyloidoses: resorption of AL-type deposits with 4'-iodo-4'-deoxydoxorubicin. Blood. 1995 Aug 1. 86(3):855-61. [QxMD MEDLINE Link]. [Full Text].
Gertz MA, Lacy MQ, Dispenzieri A, Cheson BD, Barlogie B, Kyle RA, et al. A multicenter phase II trial of 4'-iodo-4'deoxydoxorubicin (IDOX) in primary amyloidosis (AL). Amyloid. 2002 Mar. 9(1):24-30. [QxMD MEDLINE Link].
[Guideline] Dispenzieri A, Buadi F, Kumar SK, et al. Treatment of Immunoglobulin Light Chain Amyloidosis: Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Statement. Mayo Clin Proc. 2015 Aug. 90 (8):1054-81. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

The relationship among light chain–type amyloidosis (AL), the other monoclonal plasma cell disorders, and the other amyloidoses. Ig = immunoglobulin; MGUS = monoclonal gammopathy of undetermined significance.

of 1

Author

Slavomir Urbancek, MD, PhD Head, Department of Dermatology, FD Roosevelt Hospital, Slovakia; Member of executive commitee - Slovak Dermatovenereological Society

Slavomir Urbancek, MD, PhD is a member of the following medical societies: American Academy of Dermatology, European Academy of Dermatology and Venereology, Slovakian Dermatovenerological Society, Slovak Society of Allergology and Clinical Immunology

Disclosure: Received honoraria from Abbott for speaking and teaching; Received honoraria from Pfizer for none; Received honoraria from Janssen for speaking and teaching; Received honoraria from MSD for speaking and teaching; Received consulting fee from Roche for speaking and teaching.

Coauthor(s)

Pere Gascon, MD, PhD Professor and Senior Consultant, Division of Medical Oncology, Institute of Hematology and Medical Oncology, Hospital Clinic; Director, Laboratory of Molecular and Translational Oncology, University of Barcelona Faculty of Biology, Spain

Pere Gascon, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, New York Academy of Medicine, New York Academy of Sciences, Royal College of Surgeons of Edinburgh, Royal European Academy of Doctors, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Daniel R Jacobson, MD Professor of Medicine, Boston University School of Medicine; Chief of Oncology, Veterans Affairs Boston Healthcare System

Disclosure: Nothing to disclose.

Carol A Bogdan, MD Consultant in Hematology-Oncology, Myrtle Beach, SC

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Lawrence H Brent, MD Associate Professor of Medicine, Sidney Kimmel Medical College of Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center

Lawrence H Brent, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Physicians, American College of Rheumatology

Disclosure: Stock ownership for: Johnson & Johnson.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Robert E Wolf, MD, PhD Professor Emeritus, Department of Medicine, Louisiana State University School of Medicine in Shreveport; Chief, Rheumatology Section, Medical Service, Overton Brooks Veterans Affairs Medical Center

Robert E Wolf, MD, PhD is a member of the following medical societies: American College of Rheumatology, Arthritis Foundation, Society for Leukocyte Biology

Disclosure: Nothing to disclose.

Joel N Buxbaum, MD Professor, Department of Molecular and Experimental Medicine, The Scripps Research Institute

Joel N Buxbaum, MD is a member of the following medical societies: American Association for the Advancement of Science, American Society for Clinical Investigation, American Society of Human Genetics, Association of American Physicians, Association of Black Cardiologists, Henry Kunkel Society

Disclosure: Received consulting fee from Foldrx pharmaceuticals for consulting; Received consulting fee from Isis pharmaceuticals for consulting; Received consulting fee from alnylam pharmaceutical for consulting; Received consulting fee from Pfizer Pharmaceuticals for consulting.