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Medicina & Laboratorio

2023, Number 4

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Medicina & Laboratorio 2023; 27 (4)

Systemic amyloidosis with emphasis on immunoglobulin light chain amyloidosis

Gálvez-Cárdenas KM

Language: Spanish
References: 61
Page: 395-409
PDF size: 385.63 Kb.


ABSTRACT

Systemic amyloidosis is a rare disease in which a misfolded protein becomes resistant to catabolic processes in the body, leading to the formation of fibrils that are deposited extracellularly within tissues, causing organ dysfunction and death. Amyloidosis is a multisystem disorder that can affect the heart, kidneys, nerves, liver, lungs, and gastrointestinal tract. It results in a high symptom burden, impaired quality of life, and shorter survival. The three most important types that account for 90% of the cases are: immunoglobulin light chain amyloidosis (AL), secondary reactive amyloidosis (AA), and transthyretin amyloidosis (ATTR). This article is focused on AL amyloidosis, emphasizing on when this disease should be suspected, the most frequent clinical findings, how the diagnosis is confirmed, and the different treatment options that are available.


REFERENCES

  1. Iadanza MG, Jackson MP, Hewitt EW, RansonNA, Radford SE. A new era for understandingamyloid structures and disease. Nat RevMol Cell Biol 2018;19:755-773. https://doi.org/10.1038/s41580-018-0060-8.

  2. Wechalekar AD, Gillmore JD, Hawkins PN. Systemicamyloidosis. Lancet 2016;387:2641-2654.https://doi.org/10.1016/s0140-6736(15)01274-x.

  3. Wisniowski B, McLeod DSA, Adams R, HarveyY, Brown I, McGuire L, et al. The epidemiologyof amyloidosis in Queensland, Australia.Br J Haematol 2019;186:829-836. https://doi.org/10.1111/bjh.16000.

  4. Kyle RA, Larson DR, Kurtin PJ, Kumar S,Cerhan JR, Therneau TM, et al. Incidenceof AL amyloidosis in Olmsted County, Minnesota,1990 through 2015. Mayo Clin Proc2019;94:465-471. https://doi.org/10.1016/j.mayocp.2018.08.041.

  5. Wechalekar AD, Gillmore JD, Foard D. 25years of systemicamyloidosis. In: HazenbergPB, ed. International amyloidosis symposium.Groningen: Netherland; 2012.

  6. Díaz-Villanueva JF, Díaz-Molina R,García-González V. Protein folding andmechanisms of proteostasis. Int J MolSci 2015;16:17193-17230. https://doi.org/10.3390/ijms160817193.

  7. Kundu D, Prerna K, Chaurasia R, Bharty MK,Dubey VK. Advances in protein misfolding,amyloidosis and its correlation with humandiseases. 3 Biotech 2020;10:193. https://doi.org/10.1007/s13205-020-2166-x.

  8. Knowles TP, Vendruscolo M, Dobson CM.The amyloid state and its association with proteinmisfolding diseases. Nat Rev Mol Cell Biol2014;15:384-396. https://doi.org/10.1038/nrm3810.

  9. Muchtar E, Dispenzieri A, Magen H, GroganM, Mauermann M, McPhail ED, et al. Systemicamyloidosis from A (AA) to T (ATTR): a review. JIntern Med 2021;289:268-292. https://doi.org/https://doi.org/10.1111/joim.13169.

  10. Merlini G. AL amyloidosis: from molecular mechanismsto targeted therapies. Hematology AmSoc Hematol Educ Program 2017;2017:1-12.https://doi.org/10.1182/asheducation-2017.1.1.

  11. Fotiou D, Dimopoulos MA, Kastritis E. SystemicAL amyloidosis: Current approachesto diagnosis and management. Hemasphere2020;4:e454. https://doi.org/10.1097/hs9.0000000000000454.

  12. Bou-Zerdan M, Nasr L, Khalid F, Allam S,Bouferraa Y, Batool S, et al. Systemic ALamyloidosis: current approach and future direction.Oncotarget 2023;14:384-394. https://doi.org/10.18632/oncotarget.28415.

  13. Madan S, Dispenzieri A, Lacy MQ, BuadiF, Hayman SR, Zeldenrust SR, et al. Clinicalfeatures and treatment response of lightchain (AL) amyloidosis diagnosed in patientswith previous diagnosis of multiple myeloma.Mayo Clin Proc 2010;85:232-238. https://doi.org/10.4065/mcp.2009.0547.

  14. Kourelis TV, Gertz M, Zent C, Lacy M, KyleR, Kapoor P, et al. Systemic amyloidosis associatedwith chronic lymphocytic leukemia/small lymphocytic lymphoma. Am J Hematol2013;88:375-378. https://doi.org/10.1002/ajh.23413.

  15. De la Torre A, Reece D, Crump M, AtenafuEG, Chen C, Prica A, et al. Light chain amyloidosis(AL) associated with B cell lymphomaa single center experience. Clin LymphomaMyeloma Leuk 2021;21:e946-e959. https://doi.org/10.1016/j.clml.2021.07.003.

  16. Berkowitz C, Dittus C. Diagnosis and managementof AL amyloidosis due to Bcellnon-Hodgkin lymphoma. Front Oncol2022;12:915420. https://doi.org/10.3389/fonc.2022.915420.

  17. van de Donk NW, Mutis T, Poddighe PJ,Lokhorst HM, Zweegman S. Diagnosis, riskstratification and management of monoclonalgammopathy of undetermined significanceand smoldering multiple myeloma. Int JLab Hematol 2016;38:110-122. https://doi.org/10.1111/ijlh.12504.

  18. Milani P, Merlini G, Palladini G. Light chainamyloidosis. Mediterr J Hematol Infect Dis2018;10:e2018022. https://doi.org/10.4084/mjhid.2018.022.

  19. Palladini G, Merlini G. What is new in diagnosisand management of light chain amyloidosis?Blood 2016;128:159-168. https://doi.org/10.1182/blood-2016-01-629790.

  20. Sidiqi MH, Aljama MA, Muchtar E, Buadi FK,Warsame R, Lacy MQ, et al. Light chain typepredicts organ involvement and survival in ALamyloidosis patients receiving stem cell transplantation.Blood Adv 2018;2:769-776. https://doi.org/10.1182/bloodadvances.2018016782.

  21. Merlini G, Stone MJ. Dangerous small B-cellclones. Blood 2006;108:2520-2530. https://doi.org/10.1182/blood-2006-03-001164.

  22. Merlini G, Dispenzieri A, Sanchorawala V,Schönland SO, Palladini G, Hawkins PN, et al.Systemic immunoglobulin light chain amyloidosis.Nat Rev Dis Primers 2018;4:38. https://doi.org/10.1038/s41572-018-0034-3.

  23. Sikkink LA, Ramirez-Alvarado M. Cytotoxicityof amyloidogenic immunoglobulin light chainsin cell culture. Cell Death Dis 2010;1:e98.https://doi.org/10.1038/cddis.2010.75.

  24. Gertz MA, Dispenzieri A. Systemic amyloidosisrecognition, prognosis, and therapy: A systematicreview. JAMA 2020;324:79-89. https://doi.org/10.1001/jama.2020.5493.

  25. Baker KR. Light chain amyloidosis: Epidemiology,staging, and prognostication. Methodist DebakeyCardiovasc J 2022;18:27-35. https://doi.org/10.14797/mdcvj.1070.

  26. Kumar S, Dispenzieri A, Lacy MQ, Hayman SR,Buadi FK, Colby C, et al. Revised prognostic stagingsystem for light chain amyloidosis incorporatingcardiac biomarkers and serum free lightchain measurements. J Clin Oncol 2012;30:989-995. https://doi.org/10.1200/jco.2011.38.5724.

  27. Gillmore JD, Wechalekar A, Bird J, CavenaghJ, Hawkins S, Kazmi M, et al. Guidelines on thediagnosis and investigation of AL amyloidosis.Br J Haematol 2015;168:207-218. https://doi.org/10.1111/bjh.13156.

  28. Desport E, Bridoux F, Sirac C, Delbes S, BenderS, Fernandez B, et al. Al amyloidosis.Orphanet J Rare Dis 2012;7:54. https://doi.org/10.1186/1750-1172-7-54.

  29. Lacouture-Fierro JA, Mejía-Buriticá L, Ribero-Vargas DA. Amiloidosis AL: conceptos actuales.Med Lab 2022;26:119-139. https://doi.org/10.36384/01232576.572.

  30. Hasib-Sidiqi M, Gertz MA. Immunoglobulinlight chain amyloidosis diagnosis and treatmentalgorithm 2021. Blood Cancer J 2021;11:90.https://doi.org/10.1038/s41408-021-00483-7.

  31. Kyle RA, Gertz MA, Greipp PR, Witzig TE,Lust JA, Lacy MQ, et al. A trial of three regimensfor primary amyloidosis: colchicine alone,melphalan and prednisone, and melphalan,prednisone, and colchicine. N Engl J Med1997;336:1202-1207. https://doi.org/10.1056/nejm199704243361702.

  32. Gertz MA, Schonland S. Stem cell mobilizationand autologous transplant for immunoglobulinlight-chain amyloidosis. Hematol Oncol ClinNorth Am 2020;34:1133-1144. https://doi.org/10.1016/j.hoc.2020.07.007.

  33. Comenzo RL, Vosburgh E, Falk RH, SanchorawalaV, Reisinger J, Dubrey S, et al. Dose-intensive melphalan with blood stem-cellsupport for the treatment of AL (amyloid lightchain)amyloidosis: survival and responses in25 patients. Blood 1998;91:3662-3670.

  34. Moreau P, Leblond V, Bourquelot P, Facon T,Huynh A, Caillot D, et al. Prognostic factors forsurvival and response after high-dose therapyand autologous stem cell transplantation in systemicAL amyloidosis: a report on 21 patients.Br J Haematol 1998;101:766-769. https://doi.org/10.1046/j.1365-2141.1998.00772.x.

  35. Jaccard A, Moreau P, Leblond V, Leleu X,Benboubker L, Hermine O, et al. High-dosemelphalan versus melphalan plus dexamethasonefor AL amyloidosis. N Engl J Med2007;357:1083-1093. https://doi.org/10.1056/NEJMoa070484.

  36. D'Souza A, Dispenzieri A, Wirk B, Zhang MJ,Huang J, Gertz MA, et al. Improved outcomesafter autologous hematopoietic cell transplantationfor light chain amyloidosis: A Center forInternational Blood and Marrow Transplant ResearchStudy. J Clin Oncol 2015;33:3741-3749.https://doi.org/10.1200/jco.2015.62.4015.

  37. Gertz MA, Lacy MQ, Dispenzieri A, KumarSK, Dingli D, Leung N, et al. Refinement inpatient selection to reduce treatment-relatedmortality from autologous stem cell transplantationin amyloidosis. Bone Marrow Transplant2013;48:557-561. https://doi.org/10.1038/bmt.2012.170.

  38. Cordes S, Dispenzieri A, Lacy MQ, HaymanSR, Buadi FK, Dingli D, et al. Ten-year survivalafter autologous stem cell transplantationfor immunoglobulin light chain amyloidosis.Cancer 2012;118:6105-6109. https://doi.org/10.1002/cncr.27660.

  39. Lebovic D, Hoffman J, Levine BM, HassounH, Landau H, Goldsmith Y, et al. Predictorsof survival in patients with systemic light-chainamyloidosis and cardiac involvement initiallyineligible for stem cell transplantation and treatedwith oral melphalan and dexamethasone.Br J Haematol 2008;143:369-373. https://doi.org/10.1111/j.1365-2141.2008.07327.x.

  40. Kapoor P, Rajkumar SV. Multiple myelomain 2016: Fresh perspectives on treatmentand moments of clarity. Nat Rev Clin Oncol2017;14:73-74. https://doi.org/10.1038/nrclinonc.2016.221.

  41. Kumar SK, Hayman SR, Buadi FK, RoyV, Lacy MQ, Gertz MA, et al. Lenalidomide,cyclophosphamide, and dexamethasone(CRd) for light-chain amyloidosis:long-term results from a phase 2 trial. Blood2012;119:4860-4867. https://doi.org/10.1182/blood-2012-01-407791.

  42. Lee JY, Lim SH, Kim SJ, Lee GY, Lee JE,Choi JO, et al. Bortezomib, melphalan, andprednisolone combination chemotherapy fornewly diagnosed light chain (AL) amyloidosis.Amyloid 2014;21:261-266. https://doi.org/10.3109/13506129.2014.960560.

  43. Mikhael JR, Schuster SR, Jimenez-ZepedaVH, Bello N, Spong J, Reeder CB, et al. Cyclophosphamide-bortezomib-dexamethasone(CyBorD) produces rapid and complete hematologicresponse in patients with AL amyloidosis.Blood 2012;119:4391-4394. https://doi.org/10.1182/blood-2011-11-390930.

  44. Cibeira MT, Oriol A, Lahuerta JJ, Mateos MV,de la Rubia J, Hernández MT, et al. A phaseII trial of lenalidomide, dexamethasone andcyclophosphamide for newly diagnosed patientswith systemic immunoglobulin light chainamyloidosis. Br J Haematol 2015;170:804-813.https://doi.org/10.1111/bjh.13500.

  45. Palladini G, Sachchithanantham S, Milani P,Gillmore J, Foli A, Lachmann H, et al. A Europeancollaborative study of cyclophosphamide,bortezomib, and dexamethasone in upfronttreatment of systemic AL amyloidosis. Blood2015;126:612-615. https://doi.org/10.1182/blood-2015-01-620302.

  46. Manwani R, Cohen O, Sharpley F, MahmoodS, Sachchithanantham S, Foard D,et al. A prospective observational study of915 patients with systemic AL amyloidosistreated with upfront bortezomib. Blood2019;134:2271-2280. https://doi.org/10.1182/blood.2019000834.

  47. Lin P, Owens R, Tricot G, Wilson CS. Flowcytometric immunophenotypic analysisof 306 cases of multiple myeloma. Am JClin Pathol 2004;121:482-488. https://doi.org/10.1309/74r4-tb90-buwh-27jx.

  48. Sanchez L, Wang Y, Siegel DS, Wang ML. Daratumumab:a first-in-class CD38 monoclonalantibody for the treatment of multiple myeloma.J Hematol Oncol 2016;9:51. https://doi.org/10.1186/s13045-016-0283-0.

  49. Palumbo A, Chanan-Khan A, Weisel K, NookaAK, Masszi T, Beksac M, et al. Daratumumab,bortezomib, and dexamethasone for multiplemyeloma. N Engl J Med 2016;375:754-766.https://doi.org/10.1056/NEJMoa1606038.

  50. Dimopoulos MA, Oriol A, Nahi H, San-MiguelJ, Bahlis NJ, Usmani SZ, et al. Daratumumab,lenalidomide, and dexamethasone for multiplemyeloma. N Engl J Med 2016;375:1319-1331.https://doi.org/10.1056/NEJMoa1607751.

  51. Sher T, Fenton B, Akhtar A, Gertz MA.First report of safety and efficacy of daratumumabin 2 cases of advanced immunoglobulinlight chain amyloidosis. Blood2016;128:1987-1989. https://doi.org/10.1182/blood-2016-06-722496.

  52. Kimmich C, Schönland SO, Müller-Tidow C,Dittrich T, Hegenbart U. Daratumumab monotherapyin forty-eight heavily pretreatedpatients with advanced systemic light-chainamyloidosis. The XVIth International Symposiumon Amyloidosis 2018;March 26-29.

  53. Abeykoon JP, Zanwar S, Dispenzieri A,Gertz MA, Leung N, Kourelis T, et al. Daratumumab-based therapy in patients withheavily-pretreated AL amyloidosis. Leukemia2019;33:531-536. https://doi.org/10.1038/s41375-018-0262-2.

  54. Food and Drug Administration (FDA). DARZALEXFASPRO® (daratumumab and hyaluronidase-fihj) injection, for subcutaneous use.Maryland, Estados Unidos: FDA; 2020. Acceso23 de agosto de 2023. Disponible en https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761145s002lbl.pdf.

  55. European Medicines Agency. Summary ofproduct characteristics. Darzalex product-information.The Netherlands: European MedicinesAgency; 2020. Acceso 23 de agosto de 2020.Disponible en https://www.ema.europa.eu/en/documents/product-information/darzalexepar-product-information_en.pdf.

  56. CilinicaTrials.gov. A study to evaluate theefficacy and safety of daratumumab in combinationwith cyclophosphamide, bortezomiband dexamethasone (CyBorD) compared tocybord alone in newly diagnosed systemicamyloid light-chain (AL) amyloidosis. Bethesda,Estados Unidos: National Library of Medicine;2017-2023. Acceso 23 de agosto de 2023. Disponibleen https://classic.clinicaltrials.gov/ct2/show/NCT03201965.

  57. Kastritis E, Palladini G, Minnema MC,Wechalekar AD, Jaccard A, Lee HC, et al.Daratumumab-based treatment for immunoglobulinlight-chain amyloidosis. N Engl J Med2021;385:46-58. https://doi.org/10.1056/NEJMoa2028631.

  58. Kastritis E, Sanchorawala V, Merlini G, onbehalf of the ANDROMEDA study group.Subcutaneous daratumumab + bortezomib,cyclophosphamide, and dexamethasone(VCd) in patients with newly diagnosed lightchain (AL) amyloidosis: Updated results fromthe phase 3 ANDROMEDA study. J Clin Oncol2021;39:8003. https://doi.org/10.1200/JCO.2021.39.15_suppl.8003.

  59. Palladini G, Milani P. Diagnosis and treatmentof AL amyloidosis. Drugs 2023;83:203-216.https://doi.org/10.1007/s40265-022-01830-z.

  60. Mallus MT, Rizzello V. Treatment of amyloidosis:present and future. Eur Heart J Suppl2023;25:B99-b103. https://doi.org/10.1093/eurheartjsupp/suad082.

  61. Kumar SK, Callander NS, Adekola K, AndersonLD, Baljevic M, Campagnaro E, et al. Systemiclight chain amyloidosis, Version 2.2023,NCCN Clinical Practice Guidelines in Oncology.J Natl Compr Canc Netw 2023;21:67-81.




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