Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Multiple myeloma gammopathies

Systemic amyloidosis: moving into the spotlight



Systemic amyloidosis is a rare but increasingly recognised disease that is heterogeneous in presentation. Early diagnosis, whilst imperative, remains challenging but can improve prognosis and limit organ dysfunction. An increased repertoire of diagnostic imaging and histological techniques are becoming mainstream and promise to aid early diagnosis. Better risk stratification, via biomarkers and cytogenetics, has improved multidisciplinary treatment decisions. The use of novel agents has improved treatment efficacy, which translates into survival benefit. Newer strategies targeting pre-deposited amyloidogenic protein are under investigation. The current paper reviews available data relating to the most recent advances in the field of systemic amyloidosis.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Imaging modalities in amyloidosis.
Fig. 2: PET imaging in amyloidosis.
Fig. 3: Suggested algorithm of investigations to diagnose amyloidosis.
Fig. 4: Novel biomarkers in AL amyloidosis: [20,21,22,23,24,25,26,27].
Fig. 5: Mass spectrometry of peripheral blood.


  1. 1.

    Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med. 2003;349:583–96.

    CAS  PubMed  Google Scholar 

  2. 2.

    Quock TP, Yan T, Chang E, Guthrie S, Broder MS. Epidemiology of AL amyloidosis: a real-world study using US claims data. Blood Adv. 2018;2:1046–53.

    PubMed  PubMed Central  Google Scholar 

  3. 3.

    Lousada I, Comenzo RL, Landau H, Guthrie S, Merlini G. Light chain amyloidosis: patient experience survey from the amyloidosis research consortium. Adv Ther. 2015;32:920–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Weiss BM, Hebreo J, Cordaro DV, Roschewski MJ, Baker TP, Abbott KC, et al. Increased serum free light chains precede the presentation of immunoglobulin light chain amyloidosis. J Clin Oncol. 2014;32:2699–704.

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    Gonzalez-Lopez E, Gallego-Delgado M, Guzzo-Merello G, de Haro-Del Moral FJ, Cobo-Marcos M, Robles C, et al. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur Heart J. 2015;36:2585–94.

    CAS  PubMed  Google Scholar 

  6. 6.

    Quarta CC, Gonzalez-Lopez E, Gilbertson JA, Botcher N, Rowczenio D, Petrie A, et al. Diagnostic sensitivity of abdominal fat aspiration in cardiac amyloidosis. Eur Heart J. 2017;38:1905–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Vrana JA, Gamez JD, Madden BJ, Theis JD, Bergen HR III, Dogan A. Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens. Blood. 2009;114:4957–9.

    CAS  PubMed  Google Scholar 

  8. 8.

    Winter M, Tholey A, Kristen A, Rocken C. MALDI mass spectrometry imaging: a novel tool for the identification and classification of amyloidosis. Proteomics. 2017;17:1700236.

  9. 9.

    Kotecha T, Martinez-Naharro A, Treibel TA, Francis R, Nordin S, Abdel-Gadir A, et al. Myocardial edema and prognosis in amyloidosis. J Am Coll Cardiol. 2018;71:2919–31.

    PubMed  Google Scholar 

  10. 10.

    Banypersad SM, Fontana M, Maestrini V, Sado DM, Captur G, Petrie A, et al. T1 mapping and survival in systemic light-chain amyloidosis. Eur Heart J. 2015;36:244–51.

    PubMed  Google Scholar 

  11. 11.

    Martinez-Naharro A, Abdel-Gadir A, Treibel TA, Zumbo G, Knight DS, Rosmini S, et al. Regression of cardiac al amyloid by cardiovascular magnetic resonance. Circulation. 2016;134:A14407.

  12. 12.

    Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. 2016;133:2404–12.

    CAS  PubMed  Google Scholar 

  13. 13.

    Quarta CC, Obici L, Guidalotti PL, Pieroni M, Longhi S, Perlini S, et al. High 99mTc-DPD myocardial uptake in a patient with apolipoprotein AI-related amyloidotic cardiomyopathy. Amyloid. 2013;20:48–51.

    PubMed  Google Scholar 

  14. 14.

    Hawkins PN. Serum amyloid P component scintigraphy for diagnosis and monitoring amyloidosis. Curr Opin Nephrol Hypertens. 2002;11:649–55.

    PubMed  Google Scholar 

  15. 15.

    Manwani R, Page J, Lane T, Burniston M, Skillen A, Lachmann HJ, et al. A pilot study demonstrating cardiac uptake with 18F-florbetapir PET in AL amyloidosis patients with cardiac involvement. Amyloid. 2018;25:247–52.

    CAS  PubMed  Google Scholar 

  16. 16.

    Ezawa N, Katoh N, Oguchi K, Yoshinaga T, Yazaki M, Sekijima Y. Visualization of multiple organ amyloid involvement in systemic amyloidosis using (11)C-PiB PET imaging. Eur J Nucl Med Mol Imaging. 2018;45:452–61.

    PubMed  Google Scholar 

  17. 17.

    Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Colby C, et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol. 2012;30:989–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Merlini G, Lousada I, Ando Y, Dispenzieri A, Gertz MA, Grogan M, et al. Rationale, application and clinical qualification for NT-proBNP as a surrogate end point in pivotal clinical trials in patients with AL amyloidosis. Leukemia. 2016;30:1979–86.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Muchtar E, Dispenzieri A, Leung N, Lacy MQ, Buadi FK, Dingli D, et al. Depth of organ response in AL amyloidosis is associated with improved survival: grading the organ response criteria. Leukemia. 2018;32:2240–9.

    PubMed  Google Scholar 

  20. 20.

    Palladini G, Barassi A, Perlini S, Milani P, Foli A, Russo P, et al. Midregional proadrenomedullin (MR-proADM) is a powerful predictor of early death in AL amyloidosis. Amyloid. 2011;18:216–21.

    CAS  PubMed  Google Scholar 

  21. 21.

    Kastritis E, Papassotiriou I, Merlini G, Milani P, Terpos E, Basset M, et al. Growth differentiation factor-15 is a new biomarker for survival and renal outcomes in light chain amyloidosis. Blood. 2018;131:1568–75.

    CAS  PubMed  Google Scholar 

  22. 22.

    Kastritis E, Gavriatopoulou M, Dimopoulos MA, Eleutherakis-Papaiakovou E, Kanellias N, Roussou M, et al. Osteoprotegerin is a significant prognostic factor for overall survival in patients with primary systemic amyloidosis independent of the Mayo staging. Blood Cancer J. 2015;5:e319.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Kastritis E, Papassotiriou I, Terpos E, Roussou M, Gavriatopoulou M, Komitopoulou A, et al. Clinical and prognostic significance of serum levels of von Willebrand factor and ADAMTS-13 antigens in AL amyloidosis. Blood. 2016;128:405–9.

    CAS  PubMed  Google Scholar 

  24. 24.

    Dispenzieri A, Gertz MA, Saenger A, Kumar SK, Lacy MQ, Buadi FK, et al. Soluble suppression of tumorigenicity 2 (sST2), but not galactin-3, adds to prognostication in patients with systemic AL amyloidosis independent of NT-proBNP and troponin T. Am J Hematol. 2015;90:524–8.

    CAS  PubMed  Google Scholar 

  25. 25.

    Abraham J, Desport E, Rigaud C, Marin B, Bender S, Lacombe C, et al. Hepatocyte growth factor measurement in AL amyloidosis. Amyloid. 2015;22:112–6.

    CAS  PubMed  Google Scholar 

  26. 26.

    Kristen AV, Rosenberg M, Lindenmaier D, Merkle C, Steen H, Andre F, et al. Osteopontin: a novel predictor of survival in patients with systemic light-chain amyloidosis. Amyloid. 2014;21:202–10.

    CAS  PubMed  Google Scholar 

  27. 27.

    Sachchithanantham S, Berlanga O, Alvi A, Mahmood SA, Lachmann HJ, Gillmore JD, et al. Immunoparesis defined by heavy+light chain suppression is a novel marker of long-term outcomes in cardiac AL amyloidosis. Br J Haematol. 2017;179:575–85.

    CAS  PubMed  Google Scholar 

  28. 28.

    Bhole MV, Sadler R, Ramasamy K. Serum-free light-chain assay: clinical utility and limitations. Ann Clin Biochem. 2014;51:528–42.

    CAS  PubMed  Google Scholar 

  29. 29.

    Milani P, Murray DL, Barnidge DR, Kohlhagen MC, Mills JR, Merlini G, et al. The utility of MASS-FIX to detect and monitor monoclonal proteins in the clinic. Am J Hematol. 2017;92:772–9.

    CAS  PubMed  Google Scholar 

  30. 30.

    Sharpley FA, Manwani R, Mahmood S, Sachchithanantham S, Lachmann HJ, Gillmore JD, et al. A novel mass spectrometry method to identify the serum monoclonal light chain component in systemic light chain amyloidosis. Blood Cancer J. 2019;9:16.

    PubMed  PubMed Central  Google Scholar 

  31. 31.

    Kourelis TV, Kumar SK, Gertz MA, Lacy MQ, Buadi FK, Hayman SR, et al. Coexistent multiple myeloma or increased bone marrow plasma cells define equally high-risk populations in patients with immunoglobulin light chain amyloidosis. J Clin Oncol. 2013;31:4319–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Sidana S, Tandon N, Dispenzieri A, Gertz MA, Dingli D, Jevremovic D, et al. Prognostic significance of circulating plasma cells by multi-parametric flow cytometry in light chain amyloidosis. Leukemia. 2018;32:1421–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Muchtar E, Dispenzieri A, Kumar SK, Ketterling RP, Dingli D, Lacy MQ, et al. Interphase fluorescence in situ hybridization in untreated AL amyloidosis has an independent prognostic impact by abnormality type and treatment category. Leukemia. 2017;31:1562–9.

    CAS  PubMed  Google Scholar 

  34. 34.

    Bochtler T, Hegenbart U, Kunz C, Benner A, Kimmich C, Seckinger A, et al. Prognostic impact of cytogenetic aberrations in AL amyloidosis patients after high-dose melphalan: a long-term follow-up study. Blood. 2016;128:594–602.

    CAS  PubMed  Google Scholar 

  35. 35.

    Bochtler T, Hegenbart U, Kunz C, Benner A, Seckinger A, Dietrich S, et al. Gain of chromosome 1q21 is an independent adverse prognostic factor in light chain amyloidosis patients treated with melphalan/dexamethasone. Amyloid. 2014;21:9–17.

    CAS  PubMed  Google Scholar 

  36. 36.

    Walker BA, Rowczienio D, Boyle EM, Wardell CP, Sachchithanantham S, Baginska A, et al. Exome sequencing to define a genetic signature of plasma cells in systemic al amyloidosis. Blood. 2013;122:3098.

  37. 37.

    Huang XF, Jian S, Lu JL, Shen KN, Feng J, Zhang CL, et al. Genomic profiling in amyloid light-chain amyloidosis reveals mutation profiles associated with overall survival. Amyloid. 2020;27:36–44.

  38. 38.

    da Silva Filho MI, Forsti A, Weinhold N, Meziane I, Campo C, Huhn S, et al. Genome-wide association study of immunoglobulin light chain amyloidosis in three patient cohorts: comparison with myeloma. Leukemia. 2017;31:1735–42.

    PubMed  Google Scholar 

  39. 39.

    Manwani R, Foard D, Mahmood S, Sachchithanantham S, Lane T, Quarta C, et al. Rapid hematologic responses improve outcomes in patients with very advanced (stage IIIb) cardiac immunoglobulin light chain amyloidosis. Haematologica. 2018;103:e165–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Muchtar E, Dispenzieri A, Leung N, Lacy MQ, Buadi FK, Dingli D, et al. Optimizing deep response assessment for AL amyloidosis using involved free light chain level at end of therapy: failure of the serum free light chain ratio. Leukemia. 2019;33:527–31.

    CAS  PubMed  Google Scholar 

  41. 41.

    Manwani R, Sharpley F, Mahmood S, Sachchithanantham S, Lachmann H, Gillmore J, et al. Achieving a difference in involved and uninvolved light chains (dFLC) of less than 10mg/L is the new goal of therapy in systemic AL amyloidosis: analysis of 916 patients treated upfront with bortezomib-based therapy. Blood. 2018;132:3262.

    Google Scholar 

  42. 42.

    Muchtar E, Jevremovic D, Dispenzieri A, Dingli D, Buadi FK, Lacy MQ, et al. The prognostic value of multiparametric flow cytometry in AL amyloidosis at diagnosis and at the end of first-line treatment. Blood. 2017;129:82–7.

    CAS  PubMed  Google Scholar 

  43. 43.

    Sidana S, Tandon N, Dispenzieri A, Gertz MA, Rajkumar SV, Kumar SK. The importance of bone marrow examination in patients with light chain amyloidosis achieving a complete response. Leukemia. 2018;32:1243–6.

    PubMed  Google Scholar 

  44. 44.

    Palladini GMM, Basset M, Russo F, Milani P, Foli A, Merlini G. Persistence of minimal residual disease by multiparameter flow cytometry can hinder recovery of organ damage in patients with AL amyloidosis otherwise in complete response. Blood. 2016;128:3261.

    Google Scholar 

  45. 45.

    D’Souza A, Dispenzieri A, Wirk B, Zhang MJ, Huang J, Gertz MA, et al. Improved outcomes after autologous hematopoietic cell transplantation for light chain amyloidosis: a center for international blood and marrow transplant research study. J Clin Oncol. 2015;33:3741–9.

    PubMed  PubMed Central  Google Scholar 

  46. 46.

    Sharpley F, Petrie, A, Mahmood, S, Sachchithanantham, S, Lachmann, HJ, Gillmore, JD, et al. A twenty-four year experience of autologous stem cell transplantation for light chain amyloidosis patients in the United Kingdom. Br J Haematol. 2019;187:642–52.

  47. 47.

    Sanchorawala V, Sun FG, Quillen K, Sloan JM, Berk JL, Seldin DC. Long-term outcome of patients with AL amyloidosis treated with high-dose melphalan and stem cell transplantation: 20-year experience. Blood. 2015;126:2345–7.

    PubMed  Google Scholar 

  48. 48.

    Sanchorawala V, Brauneis D, Shelton AC, Lo S, Sun FG, Sloan JM, et al. Induction therapy with bortezomib followed by bortezomib-high dose melphalan and stem cell transplantation for light chain annyloidosis: results of a prospective clinical trial. Biol Blood Marrow Transplant. 2015;21:1445–51.

    CAS  PubMed  Google Scholar 

  49. 49.

    Manwani R, Hegenbart U, Mahmood S, Sachchithanantham S, Kyriakou C, Yong K, et al. Deferred autologous stem cell transplantation in systemic AL amyloidosis. Blood Cancer J. 2018;8:101.

  50. 50.

    Wong SW, Larivee D, Warner M, Sprague KA, Fogaren T, Comenzo RL. Stem cell transplantation in patients with systemic AL amyloidosis referred for transplant after suboptimal responses to bortezomib-based initial therapy. Bone Marrow Transplant. 2017;52:936–7.

    CAS  PubMed  Google Scholar 

  51. 51.

    Landau H, Smith M, Landry C, Chou JF, Devlin SM, Hassoun H, et al. Long-term event-free and overall survival after risk-adapted melphalan and SCT for systemic light chain amyloidosis. Leukemia. 2017;31:136–42.

    CAS  PubMed  Google Scholar 

  52. 52.

    Kastritis E, Leleu X, Arnulf B, Zamagni E, Cibeira MT, Kwok F, et al. A randomized phase III trial of melphalan and dexamethasone (MDex) versus bortezomib, melphalan and dexamethasone (BMDex) for untreated patients with AL amyloidosis. Blood. 2016;128:646.

  53. 53.

    Palladini G, Sachchithanantham S, Milani P, Gillmore J, Foli A, Lachmann H, et al. A European collaborative study of cyclophosphamide, bortezomib, and dexamethasone in upfront treatment of systemic AL amyloidosis. Blood. 2015;126:612–5.

    CAS  PubMed  Google Scholar 

  54. 54.

    Manwani R, Cohen O, Sharpley F, Mahmood S, Sachchithanantham S, Foard D, et al. A prospective observational study of 915 patients with systemic AL amyloidosis treated with upfront bortezomib. Blood. 2019;134:2271–80.

  55. 55.

    Kastritis E, Gavriatopoulou M, Roussou M, Fotiou D, Ziogas DC, Migkou M, et al. Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib. Blood Cancer J. 2017;7:e570.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Dispenzieri A, Lacy MQ, Zeldenrust SR, Hayman SR, Kumar SK, Geyer SM, et al. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood. 2007;109:465–70.

    CAS  PubMed  Google Scholar 

  57. 57.

    Sanchorawala V, Wright DG, Rosenzweig M, Finn KT, Fennessey S, Zeldis JB, et al. Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial. Blood. 2007;109:492–6.

    CAS  PubMed  Google Scholar 

  58. 58.

    Kastritis E, Gavriatopoulou M, Roussou M, Bagratuni T, Migkou M, Fotiou D, et al. Efficacy of lenalidomide as salvage therapy for patients with AL amyloidosis. Amyloid. 2018;25:234–41.

    CAS  PubMed  Google Scholar 

  59. 59.

    Dinner S, Witteles W, Afghahi A, Witteles R, Arai S, Lafayette R, et al. Lenalidomide, melphalan and dexamethasone in a population of patients with immunoglobulin light chain amyloidosis with high rates of advanced cardiac involvement. Haematologica. 2013;98:1593–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Hegenbart U, Bochtler T, Benner A, Becker N, Kimmich C, Kristen AV, et al. Lenalidomide/melphalan/dexamethasone in newly diagnosed patients with immunoglobulin light chain amyloidosis: results of a prospective phase 2 study with long-term follow up. Haematologica. 2017;102:1424–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Dispenzieri A, Buadi F, Laumann K, LaPlant B, Hayman SR, Kumar SK, et al. Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. Blood. 2012;119:5397–404.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Sanchorawala V, Shelton AC, Lo S, Varga C, Sloan JM, Seldin DC. Pomalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 1 and 2 trial. Blood. 2016;128:1059–62.

    CAS  PubMed  Google Scholar 

  63. 63.

    Palladini G, Milani P, Foli A, Basset M, Russo F, Perlini S, et al. A phase 2 trial of pomalidomide and dexamethasone rescue treatment in patients with AL amyloidosis. Blood. 2017;129:2120–3.

  64. 64.

    Sharpley FA, Manwani R, Mahmood S, Sachchithanantham S, Lachmann H, Gilmore J, et al. Real world outcomes of pomalidomide for treatment of relapsed light chain amyloidosis. Br J Haematol. 2018;183:557–63.

    CAS  PubMed  Google Scholar 

  65. 65.

    Shaulov A, Ganzel C, Benyamini N, Barshay Y, Goldschmidt N, Lavie D, et al. Progressive refractory light chain amyloidosis and multiple myeloma patients are responsive to the addition of clarithromycin to IMiD based therapy. Am J Hematol. 2017;92:131–5.

    CAS  PubMed  Google Scholar 

  66. 66.

    Puig NHM, Rosinol Dachs L, Gonzalez Garcia E, De Arriba F, Oriol A, Gonzalez-Calle V, et al. Randomized trial of lenalidomide and dexamethasone versus clarythromycin, lenalidomide and dexamethasone as first line treatment in patients with multiple myeloma not candidates for autologous stem cell transplantation: results of the GEM-Claridex clinical trial. Orlando, USA: American Society of Haematology; 2019.

  67. 67.

    Cohen AD, Landau H, Scott EC, Liedtke M, Kaufman JL, Rosenzweig M, et al. Safety and efficacy of carfilzomib (CFZ) in previously-treated systemic light-chain (AL) amyloidosis. Blood. 2016;128:645.

  68. 68.

    Garg MHA, Jenner M, Kishore B, Lachmann HJ, Gillmore JD, Pitchford A, et al. A phase 1 study of carfilzomib-thalidomide-dexamethasone in patients with relapsed/refractory AL amyloidosis—catalyst trial results. Orlando, USA: American Society of Haematology Conference; 2019.

  69. 69.

    Sanchorawala V, Palladini G, Kukreti V, Zonder JA, Cohen AD, Seldin DC, et al. A phase 1/2 study of the oral proteasome inhibitor ixazomib in relapsed or refractory AL amyloidosis. Blood. 2017;130:597–605.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. 70.

    Dispenzieri AKE, Wechalekar AD, Schonland SO, Kim K, Sanchorawala V, Landau HJ, et al. Primary results from the phase 3 tourmaline-AL1 trial of ixazomib-dexamethasone versus physician’s choice of therapy in patients (Pts) with relapsed/refractory primary systemic AL amyloidosis (RRAL). Orlando, FL, USA: American Society of Haematology 2019.

  71. 71.

    Kaufman GP, Schrier SL, Lafayette RA, Arai S, Witteles RM, Liedtke M. Daratumumab yields rapid and deep hematologic responses in patients with heavily pretreated AL amyloidosis. Blood. 2017;130:900–2.

    CAS  PubMed  Google Scholar 

  72. 72.

    Abeykoon JP, Zanwar S, Dispenzieri A, Gertz MA, Leung N, Kourelis T, et al. Daratumumab-based therapy in patients with heavily-pretreated AL amyloidosis. Leukemia. 2019;33:531–6.

    PubMed  Google Scholar 

  73. 73.

    Comenzo RL, Kastritis E, Maurer M, Zonder J, Minnema MC, Wechalekar A, et al. Subcutaneous daratumumab + cyclophosphamide, bortezomib, and dexamethasone (cybord) in patients with newly diagnosed amyloid light chain (AL) amyloidosis: updated safety run-in results of andromeda. Amsterdam: European Haematology Assocation; 2019.

  74. 74.

    Sidiqi MH, Saleh AS Al, Leung N, Alijama M, Jevremovic D, Gonslaves W, et al. Venetoclax for the treatment of translocation (11; 14) Al amyloidosis. Amsterdam: European Haematology Association; 2019.

  75. 75.

    Premkumar V, Comenzo R, Lentzsch S. Venetoclax in immunoglobulin light chain amyloidosis: is this the beginning or the end? Clin Lymphoma Myeloma Leuk. 2019;19:686–8.

  76. 76.

    Le Bras FDJ, Lemonnier F, Oghina S, Bodez S, Ladaique A, Maarek A, et al. Venetoclax induces sustained complete responses in refractory/relapsed patients with cardiac AL amyloidosis. J Clin Oncol. 2019;37:e19538.

  77. 77.

    Zago W, Renz M, Torres R, Dolan PJ, Barbour RM, Salmans JR, et al. NEOD001 specifically binds aggregated light chain infiltrates in multiple organs from patients with AL amyloidosis and promotes phagocytic clearance of AL aggregates in vitro. Blood. 2015;126:3016.

  78. 78.

    Gibbs SDJ, De Cruz M, Sattianayagam PT, Lachmann HJ, Gillmore JD, Hawkins PN, et al. Transient post chemotherapy rise in NT Pro-BNP in AL amyloidosis: implications for organ response assessment. Blood. 2009;114:712.

    Google Scholar 

  79. 79.

    Gertz MACA, Comenzo RL, Du Mond C, Kastritis E, Landau HJ, Libby III EL, et al. Results of the phase 3 VITAL study of NEOD001 (Birtamimab) plus standard of care in patients with light chain (AL) amyloidosis suggest survival benefit for mayo stage IV patients. Orlando, FL, USA: American Society of Haematology; 2019.

  80. 80.

    Richards DB, Cookson LM, Barton SV, Liefaard L, Lane T, Hutt DF, et al. Repeat doses of antibody to serum amyloid P component clear amyloid deposits in patients with systemic amyloidosis. Sci Transl Med. 2018;10:3128.

  81. 81.

    Edwards CV, Gould J, Langer AL, Mapara M, Radhakrishnan J, Maurer MS, et al. Interim analysis of the phase 1a/b study of chimeric fibril-reactive monoclonal antibody 11-1F4 in patients with AL amyloidosis. Amyloid. 2017;24:58–9.

    PubMed  Google Scholar 

  82. 82.

    Swuec P, Lavatelli F, Tasaki M, Paissoni C, Rognoni P, Maritan M, et al. Cryo-EM structure of cardiac amyloid fibrils from an immunoglobulin light chain AL amyloidosis patient. Nat Commun. 2019;10:1269.

    PubMed  PubMed Central  Google Scholar 

  83. 83.

    Radamaker L, Lin YH, Annamalai K, Huhn S, Hegenbart U, Schonland SO, et al. Cryo-EM structure of a light chain-derived amyloid fibril from a patient with systemic AL amyloidosis. Nat Commun. 2019;10:1103.

    PubMed  PubMed Central  Google Scholar 

  84. 84.

    Wechalekar AD, Whelan C. Encouraging impact of doxycycline on early mortality in cardiac light chain (AL) amyloidosis. Blood Cancer J. 2017;7:e546.

  85. 85.

    Ericzon BG, Wilczek HE, Larsson M, Wijayatunga P, Stangou A, Pena JR, et al. Liver transplantation for hereditary transthyretin amyloidosis: after 20 years still the best therapeutic alternative? Transplantation. 2015;99:1847–54.

    CAS  PubMed  Google Scholar 

  86. 86.

    Berk JL, Suhr OB, Obici L, Sekijima Y, Zeldenrust SR, Yamashita T, et al. Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial. JAMA. 2013;310:2658–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. 87.

    Merkies IS. Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial. Neurology. 2013;80:1444–5.

    PubMed  Google Scholar 

  88. 88.

    Adams D, Gonzalez-Duarte A, O’Riordan WD, Yang CC, Ueda M, Kristen AV, et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N Engl J Med. 2018;379:11–21.

    CAS  PubMed  Google Scholar 

  89. 89.

    Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK, et al. Inotersen treatment for patients with hereditary transthyretin amyloidosis. N Engl J Med. 2018;379:22–31.

    CAS  PubMed  Google Scholar 

  90. 90.

    Solomon SD, Adams D, Kristen A, Grogan M, Gonzalez-Duarte A, Maurer MS, et al. Effects of patisiran, an RNA interference therapeutic, on cardiac parameters in patients with hereditary transthyretin-mediated amyloidosis. Circulation. 2019;139:431–43.

    CAS  PubMed  Google Scholar 

  91. 91.

    Morgan GJ, Yan NL, Mortenson DE, Rennella E, Blundon JM, Gwin RM, et al. Stabilization of amyloidogenic immunoglobulin light chains by small molecules. Proc Natl Acad Sci USA. 2019;116:8360–9.

    CAS  PubMed  Google Scholar 

  92. 92.

    Hovey BM, Ward JE, Soo Hoo P, O’Hara CJ, Connors LH, Seldin DC. Preclinical development of siRNA therapeutics for AL amyloidosis. Gene Ther. 2011;18:1150–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. 93.

    Wechalekar AD, Gillmore JD, Hawkins PN. Systemic amyloidosis. Lancet. 2016;387:2641–54.

    CAS  PubMed  Google Scholar 

  94. 94.

    Kaku M, Berk JL. Neuropathy associated with systemic amyloidosis. Semin Neurol. 2019;39:578–88.

    PubMed  Google Scholar 

  95. 95.

    Westermark GT, Fandrich M, Westermark P. AA amyloidosis: pathogenesis and targeted therapy. Annu Rev Pathol. 2015;10:321–44.

    CAS  PubMed  Google Scholar 

  96. 96.

    Sethi S, Theis JD. Pathology and diagnosis of renal non-AL amyloidosis. J Nephrol. 2018;31:343–50.

    CAS  PubMed  Google Scholar 

  97. 97.

    Sidiqi MH, Aljama MA, Buadi FK, Warsame RM, Lacy MQ, Dispenzieri A, et al. Stem cell transplantation for light chain amyloidosis: decreased early mortality over time. J Clin Oncol. 2018;36:1323–9.

    PubMed  Google Scholar 

  98. 98.

    Palladini G, Milani P, Foli A, Vidus Rosin M, Basset M, Lavatelli F, et al. Melphalan and dexamethasone with or without bortezomib in newly diagnosed AL amyloidosis: a matched case-control study on 174 patients. Leukemia. 2014;28:2311–6.

    CAS  PubMed  Google Scholar 

  99. 99.

    Wechalekar AD, Goodman HJB, Lachmann HJ, Offer M, Hawkins PN, Gillmore JD. Safety and efficacy of risk-adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL amyloidosis. Blood. 2007;109:457–64.

    CAS  PubMed  Google Scholar 

  100. 100.

    Mahmood S, Venner CP, Sachchithanantham S, Lane T, Rannigan L, Foard D, et al. Lenalidomide and dexamethasone for systemic AL amyloidosis following prior treatment with thalidomide or bortezomib regimens. Br J Haematol. 2014;166:842–8.

    CAS  PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Ashutosh D. Wechalekar.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Cohen, O.C., Wechalekar, A.D. Systemic amyloidosis: moving into the spotlight. Leukemia 34, 1215–1228 (2020).

Download citation

Further reading


Quick links