Managing AL and ATTR Amyloidosis

CE / CME

Advances in Systemic Amyloidosis: A Spotlight on New Disease-Modifying Therapies Across the Clinical Spectrum

Pharmacists: 1.25 contact hours (0.125 CEUs)

Physicians: Maximum of 1.25 AMA PRA Category 1 Credits

Nurses: 1.25 Nursing contact hours

Released: October 21, 2021

Expiration: October 20, 2022

Beth Faiman
Beth Faiman, PhD, MSN, APN-BC, AOCN, BMTCN, FAAN, FAPO
Shaji K. Kumar
Shaji K. Kumar, MD

Activity

Progress
1
Course Completed
References

  1. Sugi MD, Kawashima A, Salomao MA, et al. Amyloidosis: multisystem spectrum of disease with pathologic correlation. Radiographics. 2021;[Epub ahead of print].
  2. Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med. 2003;349:583-596.
  3. Picken MM. The pathology of amyloidosis in classification: a review. Acta Haematol. 2020;143:322-334.
  4. Gertz MA, Dispenzieri A. Systemic amyloidosis recognition, prognosis, and therapy: a systematic review. JAMA. 2020;324:79-89.
  5. Muchtar E, Dispenzieri A, Magen H, et al. Systemic amyloidosis from A (AA) to T (ATTR): a review. J Intern Med. 2021;289:268-292.
  6. Theis JD, Dasari S, Vrana JA, et al. Shotgun-proteomics-based clinical testing for diagnosis and classification of amyloidosis. J Mass Spectrom. 2013;48:1067-1077.
  7. Vrana JA, Gamez JD, Madden B, et al. Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens. Blood. 2009;114:4957-4959.
  8. Gillmore JD, Wechalekar A, Bird J, et al. Guidelines on the diagnosis and investigation of AL amyloidosis. Br J Haematol. 2015;168:207-218.
  9. Dasari S, Theis JD, Vrana JA, et al. Amyloid typing by mass spectrometry in clinical practice: a comprehensive review of 16,175 samples. Mayo Clin Proc. 2020;95:1852-1864.
  10. Glavey SV, Leung N. Monoclonal gammopathy: The good, the bad and the ugly. Blood Rev. 2016;30:223-231.
  11. Kyle RA, Remstein ED, Therneau TM, et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med. 2007;356:2582-2590.
  12. Hamed RA, Bazarbachi AH, Bazarbachi A, et al. Comprehensive review of AL amyloidosis: some practice recommendations. Blood Cancer J. 2021;11:97.
  13. Dispenzieri A, Kastritis E, Wechalekar AD, et al. A randomized phase 3 study of ixazomib–dexamethasone versus physician’s choice in relapsed or refractory AL amyloidosis. Leukemia. 2021;[Epub ahead of print].
  14. Baker KR, Rice L. The amyloidoses: clinical features, diagnosis and treatment. Methodist Debakey Cardiovasc J. 2012;8:3-7.
  15. Katzmann JA, Abraham RS, Dispenzieri A, et al. Diagnostic performance of quantitative kappa and lambda free light chain assays in clinical practice. Clin Chem. 2005;878-881.
  16. Merlini G. Serum free light chains in other monoclonal gammopathies. Hematology Meeting Reports. 2008;2:9.
  17. Kyriakou P, Mouselimis D, Tsarouchas A, et al. Diagnosis of cardiac amyloidosis: a systematic review on the role of imaging and biomarkers. BMC Cardiovasc Disord. 2018;18:221.
  18. Mahalingam H, Chacko BR, Irodi A, et al. Myocardial nulling pattern in cardiac amyloidosis on time of inversion scout magnetic resonance imaging sequence - a new observation of temporal variability. Indian J Radiol Imaging. 2018;28:427-432.
  19. Sanchorawala V. Light-chain (AL) amyloidosis: diagnosis and treatment. Clin J Am Soc Nephrol. 2006;1:1331-1341.
  20. Yilmaz M, Unsal A, Sokmen M, et al. Renal involvement in AA amyloidosis: clinical outcomes and survival. Kidney Blood Press Res. 2013;37:33-42.
  21. Hydes TJ, Aspinall RJ. Subacute liver failure secondary to amyloid light-chain amyloidosis. Gastroenterol Hepatol (N Y). 2012;8:205-208.
  22. Shin SC, Robinson-Papp J. Amyloid neuropathies. Mt Sinai J Med. 2012;79:733-748.
  23. 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;116:5126-5129.
  24. Petre S, Shah IA, Gilani N. Review article: gastrointestinal amyloidosis - clinical features, diagnosis and therapy. Aliment Pharmacol Ther. 2008;27:1006-1016.
  25. Kumar S, Dispenzieri A, Lacy MQ, et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol. 2012;30:989-995.
  26. Milani P, Merlini G, Palladini G. Light chain amyloidosis. Mediterr J Hematol Infect Dis. 2018;10:e2018022.
  27. Muchtar E, Therneau TM, Larson DR, et al. Comparative analysis of staging systems in AL amyloidosis. Leukemia. 2019;33:811-814.
  28. Muchtar E, Gertz MA, Kumar SK, et al. Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death. Blood. 2017;129:2111-2119.
  29. Muchtar E, Dispenzieri A, Leung N, et al. Depth of organ response in AL amyloidosis is associated with improved survival: grading the organ response criteria. Leukemia. 2018;32:2240-2249.
  30. Chung A, Kaufman GP, Sidana S, et al. Organ responses with daratumumab therapy in previously treated AL amyloidosis. Blood Adv. 2020;4:458-466.
  31. Wechalekar AD, Gillmore JD, Bird J, et al. Guidelines on the management of AL amyloidosis. Br J Haematol. 2015;168:186-206.
  32. Palladini G, Milani P, Merlini G. Management of AL amyloidosis in 2020. Blood. 2020;136:2620-2627.
  33. Fotiou D, Dimopoulos MA, Kastritis E. Systemic AL amyloidosis: current approaches to diagnosis and management. Hemasphere. 2020;4:e454.
  34. Palladini G, Dispenzieri A, Gertz MA, 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;30:4541-4549.
  35. Sidana S, Milani P, Binder M, et al. A validated composite organ and hematologic response model for early assessment of treatment outcomes in light chain amyloidosis. Blood Cancer J. 2020;10:41.
  36. Zhang KW, Stockerl-Goldstein KE, Lenihan DJ. Emerging therapeutics for the treatment of light chain and transthyretin amyloidosis. JACC Basic Transl Sci. 2019;4:438-448.
  37. Aimo A, Budda G, Fontana, M, et al. Therapies for cardiac light chain amyloidosis: an update. Int J Cardiol. 2018;271:152-160.
  38. Dispenzieri A, Kyle RA, Lacy MQ, et al. Superior survival in primary systemic amyloidosis patients undergoing peripheral blood stem cell transplantation: a case-control study. Blood. 2004;103:3960-3963.
  39. Jaccard A, Moreau P, Leblond V, et al. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med. 2007;357:1083-1093.
  40. Gertz MA, Lacy MQ, Dispenzieri A, et al. Stem cell transplantation compared with melphalan plus dexamethasone in the treatment of immunoglobulin light-chain amyloidosis. Cancer. 2016;122:2197-2205.
  41. D'Souza A, Dispenzieri A, Work B, 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;33:3741-3749.
  42. Sidana S, Sidiqi MH, Dispenzieri A, et al. Fifteen year overall survival rates after autologous stem cell transplantation for AL amyloidosis. Am J Hematol. 2019;94:1020-1026.
  43. Vaxman J, Dispenzieri A. The role of autologous stem cell transplantation in amyloidosis. Oncology (Williston Park). 2021;35:471-478.
  44. Hwa YL, Kumar SK, Gertz MA, et al. Induction therapy pre-autologous stem cell transplantation in immunoglobulin light chain amyloidosis: a retrospective evaluation. Am J Hematol. 2016;91:984-988.
  45. Vaxman J, Sidiqi MH, Al Saleh AS, et al. Depth of response prior to autologous stem cell transplantation predicts survival in light chain amyloidosis. Bone Marrow Transplant. 2021;56:928-935.
  46. Leung N, Leung TR, Cha SS, et al. Excessive fluid accumulation during stem cell mobilization: a novel prognostic factor of first-year survival after stem cell transplantation in AL amyloidosis patients. Blood. 2005;106:3353-3357.
  47. Tandon N, Muchtar E, Sidana S, et al. Revisiting conditioning dose in newly diagnosed light chain amyloidosis undergoing frontline autologous stem cell transplant: impact on response and survival. Bone Marrow Transplant. 2017;52:1126-1132.
  48. Al Saleh AS, Sidiqi MH, Sidana S, et al. Impact of consolidation therapy post autologous stem cell transplant in patients with light chain amyloidosis. Am J Hematol. 2019;94:1066-1071.
  49. Basset M, Milani P, Nuvolone M, et al. Sequential response-driven bortezomib-based therapy followed by autologous stem cell transplant in AL amyloidosis. Blood Adv. 2020;4:4175-4179.
  50. Treatment guidelines: amyloidosis. MSMART: Stratification for myeloma and risk-adapted therapy. msmart.org/treatment-guidlines. Accessed October 14, 2021.
  51. Palladini G, Perfetti V, Obici L, et al. Association of melphalan and high-dose dexamethasone is effective and well tolerated in patients with AL (primary) amyloidosis who are ineligible for stem cell transplantation. Blood. 2004;103:2936-2938.
  52. Palladini G, Russo P, Nuvolone M, et al. Treatment with oral melphalan plus dexamethasone produces long-term remissions in AL amyloidosis. Blood. 2007;110:787-788.
  53. Wechalekar AD, Lachmann HJ, Offer M, et al. Efficacy of bortezomib in systemic AL amyloidosis with relapsed/refractory clonal disease. Haematologica. 2008;93:295-298.
  54. Kastritis E, Wechalekar AD, Dimopoulos MA, et al. Bortezomib with or without dexamethasone in primary systemic (light chain) amyloidosis. J Clin Oncol. 2010;20:1031.
  55. Zonder JA, Sanchorawala V, Snyder R, et al. Melphalan and dexamethasone plus bortezomib induces hematologic and organ responses in AL-amyloidosis with tolerable neurotoxicity. Blood. 2009;114: Abstract 748.
  56. Gasparetto C, Sanchorawala V, Snyder RM, et al. Use of melphalan (M)/dexamethasone (D)/bortezomib in AL amyloidosis. J Clin Oncol. 2010;28: Abstract 8024.
  57. Mikhael JR, Schuster SR, Jimenez-Zepeda VH, et al. The combination of cyclophosphamide-bortezomib-dexamethasone (CyBor-D) is a highly effective and well tolerated regimen that produces rapid and complete hematological response in patients with AL amyloidosis. Blood. 2010;116: Abstract 3063.
  58. Kastritis E, Leleu X, Arnulf B, et al. Bortezomib, melphalan, and dexamethasone for light-chain amyloidosis. J Clin Oncol. 2020;38:3252-3260.
  59. Kastritis E, Palladini G, Minnema MC, et al. Daratumumab-based treatment for immunoglobulin light-chain amyloidosis. N Engl J Med. 2021;385:46-58.
  60. Kastritis E, Sanchorawala V, Merlini G, et al. Subcutaneous daratumumab + bortezomib, cyclophosphamide, and dexamethasone (VCd) in patients with newly diagnosed light chain (AL) amyloidosis: Updated results from the phase 3 ANDROMEDA study. J Clin Oncol. 2021;39(suppl May 20, 2021):8003.
  61. Sanchorawala V, Palladini G, Minnema HC, et al. Health-related quality of life in patients with AL amyloidosis treated with daratumumab, cyclophosphamide, bortezomib, and dexamethasone: results from the phase 3 ANDROMEDA study. Presented at: 2020 Annual Meeting of the American Society of Hematology; December 5-8, 2020. Abstract 1640.
  62. ClinicalTrials.gov. Phase 1/2, open label, dose escalation study of NEOD001 in subjects with light chain (AL) amyloidosis. clinicaltrials.gov/ct2/show/NCT01707264. Accessed October 14, 2021.
  63. Gertz M, Comenzo RL, Landau H, et al. Demonstrates organ biomarker responses in patients with light chain amyloidosis and persistent organ dysfunction: results from a phase 1/2 study. Lymphoma Myeloma Leuk. 2017;17(suppl): E22-E23.
  64. ClinicalTrials.gov. The VITAL amyloidosis study, a global phase 3, efficacy and safety study of NEOD001 in patients with AL amyloidosis (VITAL). clinicaltrials.gov/ct2/show/NCT02312206. Accessed October 14, 2021.
  65. Gertz MA, Cohen, AD, Comenzo, 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. Presented at: 2019 Annual Meeting of the American Society of Hematology; December 7-10, 2019. Abstract 3166.
  66. Dember LM. Amyloidosis-associated kidney disease. J Am Soc Nephrol. 2006;17;3458-3471.
  67. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: systemic light chain amyloidosis. v.1.2022. nccn.org. Accessed October 14, 2021.
  68. Daratumumab [prescribing information]. Horsham, PA: Janssen Biotech; 2021.
  69. Quarta CC, Kruger JL, and Falk RH. Cardiac amyloidosis. Circulation. 2012;126:e178-182.
  70. Tanskanan M, Peurlinna T, Polvikoski T. Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: a population-based autopsy study. Ann Med. 2008;40:232.
  71. Sperry BW, Reyes BA, Ikram A, et al. Tenosynovial and Cardiac Amyloidosis in Patients Undergoing Carpal Tunnel Release. Am Coll Cardiol. 2018;72:2040-2050.
  72. Gonzalez-Lopez E, Gallego-Delgado M, Guzzo-Merello G, et al. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur Heart J. 2015;36:2585-2594.
  73. Treibel TA, Fontana M, Gilbertson JA, et al. Occult transthyretin cardiac amyloid in severe calcific aortic stenosis. Circ Cardiovasc Imaging. 2016;9:e005066.
  74. Castano A, Narotsky DL, Hamid N, et al. Unveiling transthyretin cardiac amyloidosis and its predictors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. Eur Heart J. 2017;38:2879-2887.
  75. Grogan, M, Scott CG, Kyle RA, et al. Natural history of wild-type transthyretin cardiac amyloidosis and risk stratification using a novel staging system. J Am Coll Cardiol. 2016;68:1014-1020.
  76. Jacobson DR, Pastore RD, Yaghoubian R, et al. Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans. N Engl J Med. 1997;336:466-473.
  77. Rapezzi C, Quarta CC, Obici L, et al. Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype: an Italian perspective. Eur Heart J. 2013;34:520-528.
  78. Sekijima Y. Hereditary transthyretin amyloidosis. 2001 [Updated 2017]. In: Adam MP, Ardinger HH, Pagon RA, et al. eds. GeneReviews [Internet]. University of Washington, Seattle; 2017.
  79. Mints YY, Doros g, Berk JL, et al. Features of atrial fibrillation in wild-type transthyretin cardiac amyloidosis: a systemic review and clinical experience. ESCH Heart Fail. 2018;5:772-779.
  80. Plumadore E, Lombardo L, and Cabral KP. Pharmacotherapy review: emerging treatment modalities in transthyretin cardiac amyloidosis. Am J Health Syst Pharm. 2021;[Epub ahead of print].
  81. Berk JL, Suhr OB, Obici L, et al. Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial. JAMA. 2013;310:2658-2667.
  82. ClinicalTrials.gov. Study of AG10 in amyloid cardiomyopathy. clinicaltrials.gov/ct2/show/NCT03458130. Accessed October 14, 2021.
  83. Buxbaum JN. Oligonucleotide drugs for transthyretin amyloidosis. N Engl J Med. 2018;379:82-85.
  84. Matthew V and Wang AK. Inotersen: new promise for the treatment of hereditary transthyretin amyloidosis. Drug Des Devel Ther. 2019;13:1515-1525.
  85. Benson MD, Waddington-Cruz M, Berk JL, et al. Inotersen treatment for patients with hereditary transthyretin amyloidosis. N Engl J Med. 2018;379:22-31.
  86. Adams D, Gonzalez-Duarte A, O'Riordan WE, et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N Engl J Med. 2018;379:11-21.
  87. Inotersen [prescribing information]. Boston, MA: Akcea Therapeutics; 2020.
  88. Patisiran [prescribing information]. Cambridge, MA: Alnylam Pharmaceuticals; 2021.
  89. Maurer MS, Elliott P, Merlini G, et al. Design and rationale of the phase 3 ATTR-ACT clinical trial (tafamidis in transthyretin cardiomyopathy clinical trial). Circ Heart Fail. 2017;10:e003815.
  90. Damy T, Garcia-Pavia P, Mazen H, et al. Efficacy and safety of tafamidis doses in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and long-term extension study. Eur J Heart Fail. 2021;23:277-285.
  91. Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379:1007-1016.
  92. Tafamidis [prescribing information]. New York, NY: Pfizer Labs; 2019, revised 2021.
  93. Attal N. Symptomatic therapy in ATTR amyloidosis: pain killers in TTR-FAP. Orphanet J Rare Dis. 2015;10(suppl 1):I1.