Expert recommendation from the Swiss Amyloidosis Network (SAN) for systemic AL-amyloidosis (original) (raw)

Review article: Medical guidelines

Vol. 150 No. 4950 (2020)

Summary

Systemic amyloidosis is a heterogeneous group of diseases associated with protein misfolding into insoluble beta-sheet rich structures that deposit extracellularly in different organs, eventually compromising their function. There are more than 30 different proteins, known to be amyloidogenic with “light chain” (AL)-amyloidosis being the most common type, followed by transthyretin (ATTR)-, and amyloid protein A (AA)-amyloidosis. Systemic amyloidosis is a rare disease with an incidence of around 10 patients in 1 million inhabitants. Recently several new therapeutic options have been developed for subgroups of amyloidosis patients, and the introduction of novel therapies for plasma cell myeloma has led to an increase in the therapeutic armamentarium for plasma cell disorders, including AL amyloidosis. Among them, proteasome inhibitors, immunomodulatory agents (-imids), and monoclonal antibodies have been successfully introduced into clinical practice. Still, high-quality data from randomised controlled trials regarding the benefit of these cost-intensive drugs in AL amyloidosis are widely lacking, and due to the rarity of the disease many physicians will not gain routine experience in the management of these frail patients. The diagnosis of AL amyloidosis relies on a close collaboration between clinicians, pathologists, imaging experts, and sometimes geneticists. Diagnosis and treatment options in this complex disorder should be discussed in dedicated multidisciplinary boards.

In January 2020, the first meeting of the Swiss Amyloidosis Network took place in Zurich, Switzerland. One aim of this meeting was to establish a consensus guideline regarding the diagnostic work-up and the treatment recommendations for systemic amyloidosis tailored to the Swiss health care system. Forty-five participants from different fields in medicine discussed many aspects of amyloidosis. These are the Swiss Amyloidosis Network recommendations which focus on diagnostic work-up and treatment of AL-amyloidosis.

References

  1. Vaxman I, Dispenzieri A, Muchtar E, Gertz M. New developments in diagnosis, risk assessment and management in systemic amyloidosis. Blood Rev. 2020;40:100636. doi:.https://doi.org/10.1016/j.blre.2019.100636
  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(10):1046–53. doi:.https://doi.org/10.1182/bloodadvances.2018016402
  3. 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;94(3):465–71. doi:.https://doi.org/10.1016/j.mayocp.2018.08.041
  4. Palladini G, Perfetti V, Merlini G. Therapy and management of systemic AL (primary) amyloidosis. Swiss Med Wkly. 2006;136(45-46):715–20.
  5. Bochtler T, Hegenbart U, Heiss C, Benner A, Moos M, Seckinger A, et al. Hyperdiploidy is less frequent in AL amyloidosis compared with monoclonal gammopathy of undetermined significance and inversely associated with translocation t(11;14). Blood. 2011;117(14):3809–15. doi:.https://doi.org/10.1182/blood-2010-02-268987
  6. Diomede L, Rognoni P, Lavatelli F, Romeo M, di Fonzo A, Foray C, et al. Investigating heart-specific toxicity of amyloidogenic immunoglobulin light chains: A lesson from C. elegans. Worm. 2014;3(3):e965590. doi:.https://doi.org/10.4161/21624046.2014.965590
  7. Chee CE, Lacy MQ, Dogan A, Zeldenrust SR, Gertz MA. Pitfalls in the diagnosis of primary amyloidosis. Clin Lymphoma Myeloma Leuk. 2010;10(3):177–80. doi:.https://doi.org/10.3816/CLML.2010.n.027
  8. 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(25):2699–704. doi:.https://doi.org/10.1200/JCO.2013.50.0892
  9. Merlini G, Palladini G. Differential diagnosis of monoclonal gammopathy of undetermined significance. Hematology (Am Soc Hematol Educ Program). 2012;2012(1):595–603. doi:.https://doi.org/10.1182/asheducation.V2012.1.595.3798563
  10. Kyle RA, Durie BGM, Rajkumar SV, Landgren O, Blade J, Merlini G, et al.; International Myeloma Working Group. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010;24(6):1121–7. doi:.https://doi.org/10.1038/leu.2010.60
  11. Palladini G, Campana C, Klersy C, Balduini A, Vadacca G, Perfetti V, et al. Serum N-terminal pro-brain natriuretic peptide is a sensitive marker of myocardial dysfunction in AL amyloidosis. Circulation. 2003;107(19):2440–5. doi:.https://doi.org/10.1161/01.CIR.0000068314.02595.B2
  12. Siragusa S, Morice W, Gertz MA, Kyle R, Greipp PR, Lust JA, et al. Asymptomatic Amyloidosis at the Time of Diagnostic Bone Marrow Biopsy in Newly Diagnosed Patients with Multiple Myeloma and Smoldering Multiple Myeloma. Blood. 2009;114(22):2803. doi:.https://doi.org/10.1182/blood.V114.22.2803.2803
  13. Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol. 1995;32(1):45–59.
  14. Dispenzieri A, Gertz MA, Buadi F. What do I need to know about immunoglobulin light chain (AL) amyloidosis? Blood Rev. 2012;26(4):137–54. doi:.https://doi.org/10.1016/j.blre.2012.03.001
  15. Gertz MA, Comenzo R, Falk RH, Fermand JP, Hazenberg BP, Hawkins PN, et al. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18-22 April 2004. Am J Hematol. 2005;79(4):319–28. doi:.https://doi.org/10.1002/ajh.20381
  16. Westermark P. Localized AL amyloidosis: a suicidal neoplasm? Ups J Med Sci. 2012;117(2):244–50. doi:.https://doi.org/10.3109/03009734.2012.654861
  17. Hamidi Asl K, Liepnieks JJ, Nakamura M, Benson MD. Organ-specific (localized) synthesis of Ig light chain amyloid. J Immunol. 1999;162(9):5556–60.
  18. Benson MD, Buxbaum JN, Eisenberg DS, Merlini G, Saraiva MJM, Sekijima Y, et al. Amyloid nomenclature 2018: recommendations by the International Society of Amyloidosis (ISA) nomenclature committee. Amyloid. 2018;25(4):215–9. doi:.https://doi.org/10.1080/13506129.2018.1549825
  19. Garcia Y, Collins AB, Stone JR. Abdominal fat pad excisional biopsy for the diagnosis and typing of systemic amyloidosis. Hum Pathol. 2018;72:71–9. doi:.https://doi.org/10.1016/j.humpath.2017.11.001
  20. Lecadet A, Bachmeyer C, Buob D, Cez A, Georgin-Lavialle S. Minor salivary gland biopsy is more effective than normal appearing skin biopsy for amyloid detection in systemic amyloidosis: A prospective monocentric study. Eur J Intern Med. 2018;57:e20–1. doi:.https://doi.org/10.1016/j.ejim.2018.07.026
  21. Choufani EB, Sanchorawala V, Ernst T, Quillen K, Skinner M, Wright DG, et al. Acquired factor X deficiency in patients with amyloid light-chain amyloidosis: incidence, bleeding manifestations, and response to high-dose chemotherapy. Blood. 2001;97(6):1885–7. doi:.https://doi.org/10.1182/blood.V97.6.1885
  22. Thompson CA, Kyle R, Gertz M, Heit J, Pruthi R, Pardanani A. Systemic AL amyloidosis with acquired factor X deficiency: A study of perioperative bleeding risk and treatment outcomes in 60 patients. Am J Hematol. 2010;85(3):171–3. doi:.https://doi.org/10.1002/ajh.21603
  23. Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Offord JR, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med. 2006;354(13):1362–9. doi:.https://doi.org/10.1056/NEJMoa054494
  24. Phull P, Sanchorawala V, Connors LH, Doros G, Ruberg FL, Berk JL, et al. Monoclonal gammopathy of undetermined significance in systemic transthyretin amyloidosis (ATTR). Amyloid. 2018;25(1):62–7. doi:.https://doi.org/10.1080/13506129.2018.1436048
  25. Treglia G, Glaudemans AWJM, Bertagna F, Hazenberg BPC, Erba PA, Giubbini R, et al. Diagnostic accuracy of bone scintigraphy in the assessment of cardiac transthyretin-related amyloidosis: a bivariate meta-analysis. Eur J Nucl Med Mol Imaging. 2018;45(11):1945–55. doi:.https://doi.org/10.1007/s00259-018-4013-4
  26. Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. 2016;133(24):2404–12. doi:.https://doi.org/10.1161/CIRCULATIONAHA.116.021612
  27. Menter T, Bachmann M, Grieshaber S, Tzankov A. A more accurate approach to amyloid detection and subtyping: Combining in situ congo red staining and immunohistochemistry. Pathobiology. 2017;84(1):49–55. doi:.https://doi.org/10.1159/000447304
  28. Barrett CD, Dobos K, Liedtke M, Tuzovic M, Haddad F, Kobayashi Y, et al. A Changing Landscape of Mortality for Systemic Light Chain Amyloidosis. JACC Heart Fail. 2019;7(11):958–66. doi:.https://doi.org/10.1016/j.jchf.2019.07.007
  29. Wechalekar AD, Gillmore JD, Hawkins PN. Systemic amyloidosis. Lancet. 2016;387(10038):2641–54. doi:.https://doi.org/10.1016/S0140-6736(15)01274-X
  30. 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;129(15):2111–9. doi:.https://doi.org/10.1182/blood-2016-11-751628
  31. 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(9):989–95. doi:.https://doi.org/10.1200/JCO.2011.38.5724
  32. Wechalekar AD, Schonland SO, Kastritis E, Gillmore JD, Dimopoulos MA, Lane T, et al. A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. Blood. 2013;121(17):3420–7. doi:.https://doi.org/10.1182/blood-2012-12-473066
  33. Palladini G, Hegenbart U, Milani P, Kimmich C, Foli A, Ho AD, et al. A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis. Blood. 2014;124(15):2325–32. doi:.https://doi.org/10.1182/blood-2014-04-570010
  34. Fontana M, Pica S, Reant P, Abdel-Gadir A, Treibel TA, Banypersad SM, et al. Prognostic value of late gadolinium enhancement cardiovascular magnetic resonance in cardiac amyloidosis. Circulation. 2015;132(16):1570–9. doi:.https://doi.org/10.1161/CIRCULATIONAHA.115.016567
  35. 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(4):244–51. doi:.https://doi.org/10.1093/eurheartj/ehu444
  36. 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(25):2919–31. doi:.https://doi.org/10.1016/j.jacc.2018.03.536
  37. Feng J, Zhang C, Shen K, Sun J, Fang Q, Zhang L, et al. Outcome of cardiac light-chain amyloidosis in the era of novel therapy: A single-center cohort study of 227 patients. Circ J. 2019;83(4):775–82. doi:.https://doi.org/10.1253/circj.CJ-18-1048
  38. 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(34):4319–24. doi:.https://doi.org/10.1200/JCO.2013.50.8499
  39. Wong SW, Palladini G, Hegenbart U, Landau H, Warner M, Jaccard A, et al. The Finding of Del 17p in Marrow Plasma Cells from Patients with Light-Chain Amyloidosis (AL) May Confer a Worse Prognosis. Blood. 2015;126(23):3049. doi:.https://doi.org/10.1182/blood.V126.23.3049.3049
  40. 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(6):1421–6. doi:.https://doi.org/10.1038/s41375-018-0063-7
  41. He H, Liu J, Jiang H, Du J, Li L, Lu J, et al. High serum lactate dehydrogenase adds prognostic value to cardiac biomarker staging system for light chain amyloidosis. J Cancer. 2019;10(23):5622–7. doi:.https://doi.org/10.7150/jca.30345
  42. Sanchorawala V, Sun F, 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(20):2345–7. doi:.https://doi.org/10.1182/blood-2015-08-662726
  43. Rosengren S, Mellqvist UH, Nahi H, Forsberg K, Lenhoff S, Strömberg O, et al. Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation in Sweden, long-term results from all patients treated in 1994-2009. Bone Marrow Transplant. 2016;51(12):1569–72. doi:.https://doi.org/10.1038/bmt.2016.249
  44. Dittrich T, Bochtler T, Kimmich C, Becker N, Jauch A, Goldschmidt H, et al. AL amyloidosis patients with low amyloidogenic free light chain levels at first diagnosis have an excellent prognosis. Blood. 2017;130(5):632–42. doi:.https://doi.org/10.1182/blood-2017-02-767475
  45. 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(10):2240–9. doi:.https://doi.org/10.1038/s41375-018-0060-x
  46. Hayman SR, Bailey RJ, Jalal SM, Ahmann GJ, Dispenzieri A, Gertz MA, et al. Translocations involving the immunoglobulin heavy-chain locus are possible early genetic events in patients with primary systemic amyloidosis. Blood. 2001;98(7):2266–8. doi:.https://doi.org/10.1182/blood.V98.7.2266
  47. 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(7):1562–9. doi:.https://doi.org/10.1038/leu.2016.369
  48. 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(4):594–602. doi:.https://doi.org/10.1182/blood-2015-10-676361
  49. 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(1):9–17. doi:.https://doi.org/10.3109/13506129.2013.854766
  50. Palladini G, Dispenzieri A, Gertz MA, Kumar S, Wechalekar A, Hawkins PN, et al. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol. 2012;30(36):4541–9. doi:.https://doi.org/10.1200/JCO.2011.37.7614
  51. 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(10):2240–9. doi:.https://doi.org/10.1038/s41375-018-0060-x
  52. Jaccard A, Moreau P, Leblond V, Leleu X, Benboubker L, Hermine O, et al.; Myélome Autogreffe (MAG) and Intergroupe Francophone du Myélome (IFM) Intergroup. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med. 2007;357(11):1083–93. doi:.https://doi.org/10.1056/NEJMoa070484
  53. 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(13):1323–9. doi:.https://doi.org/10.1200/JCO.2017.76.9554
  54. 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(13):1323–9. doi:.https://doi.org/10.1200/JCO.2017.76.9554
  55. Gertz M, Lacy M, Dispenzieri A, Hayman S, Kumar S, Buadi F, et al. Troponin T level as an exclusion criterion for stem cell transplantation in light-chain amyloidosis. Leuk Lymphoma. 2008;49(1):36–41. doi:.https://doi.org/10.1080/10428190701684518
  56. Afrough A, Saliba RM, Hamdi A, Honhar M, Varma A, Cornelison AM, et al. Impact of Induction Therapy on the Outcome of Immunoglobulin Light Chain Amyloidosis after Autologous Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2018;24(11):2197–203. doi:.https://doi.org/10.1016/j.bbmt.2018.07.010
  57. Sanchorawala V, Skinner M, Quillen K, Finn KT, Doros G, Seldin DC. Long-term outcome of patients with AL amyloidosis treated with high-dose melphalan and stem-cell transplantation. Blood. 2007;110(10):3561–3. doi:.https://doi.org/10.1182/blood-2007-07-099481
  58. Kastritis E, Anagnostopoulos A, Roussou M, Toumanidis S, Pamboukas C, Migkou M, et al. Treatment of light chain (AL) amyloidosis with the combination of bortezomib and dexamethasone. Haematologica. 2007;92(10):1351–8. doi:.https://doi.org/10.3324/haematol.11325
  59. 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(22):646. doi:.https://doi.org/10.1182/blood.V128.22.646.646
  60. Bochtler T, Hegenbart U, Kunz C, Granzow M, Benner A, Seckinger A, et al. Translocation t(11;14) is associated with adverse outcome in patients with newly diagnosed AL amyloidosis when treated with bortezomib-based regimens. J Clin Oncol. 2015;33(12):1371–8. doi:.https://doi.org/10.1200/JCO.2014.57.4947
  61. 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(1):9–17. doi:.https://doi.org/10.3109/13506129.2013.854766
  62. 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(22):645. doi:.https://doi.org/10.1182/blood.V128.22.645.645
  63. Kastritis E, Terpos E, Roussou M, Gavriatopoulou M, Pamboukas C, Boletis I, et al. A phase 1/2 study of lenalidomide with low-dose oral cyclophosphamide and low-dose dexamethasone (RdC) in AL amyloidosis. Blood. 2012;119(23):5384–90. doi:.https://doi.org/10.1182/blood-2011-12-396903
  64. Dispenzieri A, Kastritis E, Wechalekar AD, Schönland SO, Kim K, Sanchorawala V, 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). Blood. 2019;134(Supplement_1):139. doi:.https://doi.org/10.1182/blood-2019-124409
  65. 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(2):465–70. doi:.https://doi.org/10.1182/blood-2006-07-032987
  66. Palladini G, Milani P, Foli A, Obici L, Lavatelli F, Nuvolone M, et al. Oral melphalan and dexamethasone grants extended survival with minimal toxicity in AL amyloidosis: long-term results of a risk-adapted approach. Haematologica. 2014;99(4):743–50. doi:.https://doi.org/10.3324/haematol.2013.095463
  67. Kimmich CR, Terzer T, Benner A, Dittrich T, Veelken K, Carpinteiro A, et al. Daratumumab for systemic AL amyloidosis: prognostic factors and adverse outcome with nephrotic-range albuminuria. Blood. 2020;135(18):1517–30. doi:.https://doi.org/10.1182/blood.2019003633
  68. Roussel M, Merlini G, Chevret S, Arnulf B, Stoppa AM, Perrot A, et al. A prospective phase 2 trial of daratumumab in patients with previously treated systemic light-chain amyloidosis. Blood. 2020;135(18):1531–40. doi:.https://doi.org/10.1182/blood.2019004369
  69. Sanchorawala V, Sarosiek S, Schulman A, Mistark M, Migre ME, Cruz R, et al. Safety, tolerability, and response rates of daratumumab in relapsed AL amyloidosis: results of a phase 2 study. Blood. 2020;135(18):1541–7. doi:.https://doi.org/10.1182/blood.2019004436
  70. Schwotzer R, Manz MG, Pederiva S, Waibel C, Caspar C, Lerch E, et al. Daratumumab for relapsed or refractory AL amyloidosis with high plasma cell burden. Hematol Oncol. 2019;37(5):595–600. doi:.https://doi.org/10.1002/hon.2677
  71. Roussel M, Merlini G, Chevret S, Arnulf B, Stoppa AM, Perrot A, et al. A prospective phase 2 study of daratumumab in previously-treated systemic light-chain (AL) amyloidosis. Blood. 2020;135(18):1531–40. doi:.https://doi.org/10.1182/blood.2019004369
  72. Palladini G, Kastritis E, Maurer MS, Zonder J, Minnema MC, Wechalekar AD, et al. Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA. Blood. 2020;136(1):71–80. doi:.https://doi.org/10.1182/blood.2019004460
  73. Milani P, Schönland S, Merlini G, Kimmich C, Foli A, Dittrich T, et al. Treatment of AL amyloidosis with bendamustine: a study of 122 patients. Blood. 2018;132(18):1988–91. doi:.https://doi.org/10.1182/blood-2018-04-845396
  74. 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(8):1059–62. doi:.https://doi.org/10.1182/blood-2016-04-710822
  75. Palladini G, Merlini G. Current treatment of AL amyloidosis. Haematologica. 2009;94(8):1044–8. doi:.https://doi.org/10.3324/haematol.2009.008912
  76. Leung N, Thomé SD, Dispenzieri A. Venetoclax induced a complete response in a patient with immunoglobulin light chain amyloidosis plateaued on cyclophosphamide, bortezomib and dexamethasone. Haematologica. 2018;103(3):e135–7. doi:.https://doi.org/10.3324/haematol.2017.183749
  77. Ghilardi G, Stussi G, Mazzucchelli L, Röcken C, Rossi D, Gerber B. Venetoclax plus daratumumab induce hematological CR and organ response in an AL amyloidosis patient with t(11;14). Amyloid. 2019;26(3):173–4. doi:.https://doi.org/10.1080/13506129.2019.1615428
  78. Le Bras F, Dupuis J, Lemonnier F, Oghina S, Bodez D, Ladaique A, et al. Venetoclax induces sustained complete responses in refractory/relapsed patients with cardiac AL amyloidosis. J Clin Oncol. 2019;37(15_suppl):e19538. doi:.https://doi.org/10.1200/JCO.2019.37.15_suppl.e19538
  79. Feng D, Syed IS, Martinez M, Oh JK, Jaffe AS, Grogan M, et al. Intracardiac thrombosis and anticoagulation therapy in cardiac amyloidosis. Circulation. 2009;119(18):2490–7. doi:.https://doi.org/10.1161/CIRCULATIONAHA.108.785014
  80. Rezk T, Whelan CJ, Lachmann HJ, Fontana M, Sachchithanantham S, Mahmood S, et al. Role of implantable intracardiac defibrillators in patients with cardiac immunoglobulin light chain amyloidosis. Br J Haematol. 2018;182(1):145–8. doi:.https://doi.org/10.1111/bjh.14747
  81. Grogan M, Dispenzieri A. Natural history and therapy of AL cardiac amyloidosis. Heart Fail Rev. 2015;20(2):155–62. doi:.https://doi.org/10.1007/s10741-014-9464-5
  82. Kumar SK, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Dingli D, et al. Doxycycline Used As Post Transplant Antibacterial Prophylaxis Improves Survival in Patients with Light Chain Amyloidosis Undergoing Autologous Stem Cell Transplantation. Blood. 2012;120(21):3138. doi:.https://doi.org/10.1182/blood.V120.21.3138.3138
  83. Hawkins PN, Ando Y, Dispenzeri A, Gonzalez-Duarte A, Adams D, Suhr OB. Evolving landscape in the management of transthyretin amyloidosis. Ann Med. 2015;47(8):625–38. doi:.https://doi.org/10.3109/07853890.2015.1068949
  84. Gertz MA, Landau H, Comenzo RL, Seldin D, Weiss B, Zonder J, et al. First-in-human phase I/II study of NEOD001 in patients with light chain amyloidosis and persistent organ dysfunction. J Clin Oncol. 2016;34(10):1097–103. doi:.https://doi.org/10.1200/JCO.2015.63.6530
  85. Prothena. Prothena Discontinues Development of NEOD001 for AL Amyloidosis. Press release 23 April 2018.
  86. Varga C, Lentzsch S, Comenzo RL. Beyond NEOD001 for systemic light-chain amyloidosis. Blood. 2018;132(18):1992–3. doi:.https://doi.org/10.1182/blood-2018-07-865857
  87. Richards DB, Cookson LM, Berges AC, Barton SV, Lane T, Ritter JM, et al. Therapeutic Clearance of Amyloid by Antibodies to Serum Amyloid P Component. N Engl J Med. 2015;373(12):1106–14. doi:.https://doi.org/10.1056/NEJMoa1504942
  88. Walmsley E. Press release Third quarter 2018. 2020;(October 2018):1–62.
  89. Caelum Biosciences. Alexion and Caelum Biosciences Announce Collaboration to Develop Targeted Therapy for Light Chain (AL) amyloidosis. Press release 31 January 2019.
  90. Arosio P, Vendruscolo M, Dobson CM, Knowles TPJ. Chemical kinetics for drug discovery to combat protein aggregation diseases. Trends Pharmacol Sci. 2014;35(3):127–35. doi:.https://doi.org/10.1016/j.tips.2013.12.005
  91. Palladini G, Massa M, Basset M, Russo F, Milani P, Foli A, et al. 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(22):3261. doi:.https://doi.org/10.1182/blood.V128.22.3261.3261
  92. Theodorakakou F, Fotiou D, Dimopoulos MA, Kastritis E. Solid organ transplantation in amyloidosis. Acta Haematol. 2020;143(4):352–64. doi:.https://doi.org/10.1159/000508262
  93. Angel-Korman A, Stern L, Sarosiek S, Sloan JM, Doros G, Sanchorawala V, et al. Long-term outcome of kidney transplantation in AL amyloidosis. Kidney Int. 2019;95(2):405–11. doi:.https://doi.org/10.1016/j.kint.2018.09.021
  94. Kristen AV, Kreusser MM, Blum P, Schönland SO, Frankenstein L, Dösch AO, et al. Improved outcomes after heart transplantation for cardiac amyloidosis in the modern era. J Heart Lung Transplant. 2018;37(5):611–8. doi:.https://doi.org/10.1016/j.healun.2017.11.015
  95. Grogan M, Gertz M, McCurdy A, Roeker L, Kyle R, Kushwaha S, et al. Long term outcomes of cardiac transplant for immunoglobulin light chain amyloidosis: The Mayo Clinic experience. World J Transplant. 2016;6(2):380–8. doi:.https://doi.org/10.5500/wjt.v6.i2.380
  96. Dubrey SW, Burke MM, Hawkins PN, Banner NR. Cardiac transplantation for amyloid heart disease: the United Kingdom experience. J Heart Lung Transplant. 2004;23(10):1142–53. doi:.https://doi.org/10.1016/j.healun.2003.08.027
  97. Lacy MQ, Dispenzieri A, Hayman SR, Kumar S, Kyle RA, Rajkumar SV, et al. Autologous stem cell transplant after heart transplant for light chain (Al) amyloid cardiomyopathy. J Heart Lung Transplant. 2008;27(8):823–9. doi:.https://doi.org/10.1016/j.healun.2008.05.016
  98. Gillmore JD, Goodman HJ, Lachmann HJ, Offer M, Wechalekar AD, Joshi J, et al. Sequential heart and autologous stem cell transplantation for systemic AL amyloidosis. Blood. 2006;107(3):1227–9. doi:.https://doi.org/10.1182/blood-2005-08-3253

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