Top

Published in:

Open Access 01-05-2020 | Cardiomyopathy | Cardio-oncology (MG Fradley, Section Editor)

Advances in the Treatment of Cardiac Amyloidosis

Authors: Ariane Vieira Scarlatelli Macedo, MD, MHS, Pedro Vellosa Schwartzmann, MD, PhD, Breno Moreno de Gusmão, MD, MHS, Marcelo Dantas Tavares de Melo, MD, PhD, Otávio Rizzi Coelho-Filho, MD, MPH, PhD

Published in: Current Treatment Options in Oncology | Issue 5/2020

Opinion statement

Cardiac amyloidosis is associated with a high mortality rate, a long delay between the first signs and the diagnosis but a short interval between diagnosis and death. This scenario has changed recently due to improved disease awareness among doctors and significant progress in diagnosis thanks to multimodal imaging and a multidisciplinary approach. Therefore, during the last few years, we have had access to specific therapies for those patients. Those therapies are quite different depending on the type of amyloidosis, but there has been real progress. Systemic light chain amyloidosis (AL) with cardiac involvement is the most common form of cardiac amyloidosis. The severity of heart disease dictates the prognosis in AL amyloidosis. Advances in chemotherapy and immunotherapy that suppress light chain production have improved the outcomes. These recent improvements in survival rates have enabled therapies such as implanted cardiac defibrillators and heart transplantation that were usually not indicated for patients with advanced light chain amyloid cardiomyopathy to now be applied in selected patients. For transthyretin amyloidosis (ATTR), the second most common form of amyloidosis with cardiac involvement, there is also significant progress in treatment. Until recently, we had no specific therapy for ATTR cardiomyopathy (ATTR-CM), though now disease-modifying therapies are available. Therapies that stabilize transthyretin, such as tafamidis, have been shown to improve outcomes for patients with ATTR-CM. Modern treatments that stop the synthesis of TTR through gene silencing, such as patisiran and inotersen, have shown positive results for patients with TTR amyloidosis. Significant progress has been made in the treatment of amyloid cardiomyopathy, and hopefully, we will see even more progress with the spread of those treatments. We now can be optimistic about patients with this disease.

Wechalekar AD, Gillmore JD, Hawkins PN. Systemic amyloidosis. Lancet. 2016;387(10038):2641–54.PubMedCrossRef

Bodez D, Galat A, Guellich A, Deux JF, Rosso J, Le Bras F, et al. Cardiac amyloidosis: how to recognize them and manage them? Presse Med. 2016;45(10):845–55. https://doi.org/10.1016/j.lpm.2016.07.001.PubMedCrossRef

Mohty D, Damy T, Cosnay P, Echahidi N, Casset-Senon D, Virot P, et al. Cardiac amyloidosis: updates in diagnosis and management. Arch Cardiovasc Dis. 2013;106(10):528–40. https://doi.org/10.1016/j.acvd.2013.06.051.PubMedCrossRef

Zhang KW, Stockerl-Goldstein KE, Lenihan DJ. Emerging therapeutics for the treatment of light chain and transthyretin amyloidosis. JACC Basic Transl Sci. 2019;4(3):438–48. https://doi.org/10.1016/j.jacbts.2019.02.002.PubMedPubMedCentralCrossRef

Hoigne P, Attenhofer Jost CH, Duru F, Oechslin EN, Seifert B, Widmer U, et al. Simple criteria for differentiation of Fabry disease from amyloid heart disease and other causes of left ventricular hypertrophy. Int J Cardiol. 2006;111(3):413–22. https://doi.org/10.1016/j.ijcard.2005.08.023.PubMedCrossRef

Merlini G, Palladini G. Light chain amyloidosis: the heart of the problem. Haematologica. 2013;98(10):1492–5. https://doi.org/10.3324/haematol.2013.094482.PubMedPubMedCentralCrossRef

Ruberg FL, Berk JL. Transthyretin (TTR) cardiac amyloidosis. Circulation. 2012;126(10):1286–300. https://doi.org/10.1161/CIRCULATIONAHA.111.078915.PubMedPubMedCentralCrossRef

Sipe JD, Benson MD, Buxbaum JN, Ikeda SI, Merlini G, Saraiva MJ, et al. Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines. Amyloid. 2016;23(4):209–13. https://doi.org/10.1080/13506129.2016.1257986.PubMedCrossRef

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(24):1905–8. https://doi.org/10.1093/eurheartj/ehx047.PubMedPubMedCentralCrossRef

10.

Lee SP, Park JB, Kim HK, Kim YJ, Grogan M, Sohn DW. Contemporary imaging diagnosis of cardiac amyloidosis. J Cardiovasc Imaging. 2019;27(1):1–10. https://doi.org/10.4250/jcvi.2019.27.e9.PubMedPubMedCentralCrossRef

11.

Maurer MS, Bokhari S, Damy T, Dorbala S, Drachman BM, Fontana M, et al. Expert consensus recommendations for the suspicion and diagnosis of transthyretin cardiac amyloidosis. Circ Heart Fail. 2019;12(9):e006075. https://doi.org/10.1161/CIRCHEARTFAILURE.119.006075.PubMedCrossRef

12.

Maceira AM, Joshi J, Prasad SK, Moon JC, Perugini E, Harding I, et al. Cardiovascular magnetic resonance in cardiac amyloidosis. Circulation. 2005;111(2):186–93. https://doi.org/10.1161/01.CIR.0000152819.97857.9D.PubMedCrossRef

13.

Zhao L, Tian Z, Fang Q. Diagnostic accuracy of cardiovascular magnetic resonance for patients with suspected cardiac amyloidosis: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2016;16:129. https://doi.org/10.1186/s12872-016-0311-6.PubMedPubMedCentralCrossRef

14.

Martinez-Naharro A, Treibel TA, Abdel-Gadir A, Bulluck H, Zumbo G, Knight DS, et al. Magnetic resonance in transthyretin cardiac amyloidosis. J Am Coll Cardiol. 2017;70(4):466–77. https://doi.org/10.1016/j.jacc.2017.05.053.PubMedCrossRef

15.

VanAntwerp JD, O’Mara RE, Pitt MJ, Walsh S. Technetium-99m-diphosphonate accumulation in amyloid. J Nucl Med. 1975;16(3):238–40.PubMed

16.

Damy T, Deux J-F, Moutereau S, Guendouz S, Mohty D, Rappeneau S, et al. Role of natriuretic peptide to predict cardiac abnormalities in patients with hereditary transthyretin amyloidosis. Amyloid. 2013;20(4):212–20.PubMedCrossRef

17.

Grogan M, Scott CG, Kyle RA, Zeldenrust SR, Gertz MA, Lin G, et al. Natural history of wild-type transthyretin cardiac amyloidosis and risk stratification using a novel staging system. J Am Coll Cardiol. 2016;68(10):1014–20.PubMedCrossRef

18.

Gillmore JD, Damy T, Fontana M, Hutchinson M, Lachmann HJ, Martinez-Naharro A, et al. A new staging system for cardiac transthyretin amyloidosis. Eur Heart J. 2017;39(30):2799–806.CrossRef

19.

Cappelli F, Baldasseroni S, Bergesio F, Perlini S, Salinaro F, Padeletti L, et al. Echocardiographic and biohumoral characteristics in patients with AL and TTR amyloidosis at diagnosis. Clin Cardiol. 2015;38(2):69–75.PubMedPubMedCentralCrossRef

20.

Phelan D, Collier P, Thavendiranathan P, Popovic ZB, Hanna M, Plana JC, et al. Relative apical sparing of longitudinal strain using two-dimensional speckle-tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis. Heart. 2012;98(19):1442–8. https://doi.org/10.1136/heartjnl-2012-302353.PubMedCrossRef

21.

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. https://doi.org/10.1161/CIRCULATIONAHA.108.785014.PubMedCrossRef

22.

Pagourelias ED, Mirea O, Vovas G, Duchenne J, Michalski B, Van Cleemput J, et al. Relation of regional myocardial structure and function in hypertrophic cardiomyopathy and amyloidois: a combined two-dimensional speckle tracking and cardiovascular magnetic resonance analysis. Eur Heart J Cardiovasc Imaging. 2019;20(4):426–37. https://doi.org/10.1093/ehjci/jey107.PubMedCrossRef

23.

White JA, Kim HW, Shah D, Fine N, Kim KY, Wendell DC, et al. CMR imaging with rapid visual T1 assessment predicts mortality in patients suspected of cardiac amyloidosis. J Am Coll Cardiol Img. 2014;7(2):143–56. https://doi.org/10.1016/j.jcmg.2013.09.019.CrossRef

24.

Mongeon FP, Jerosch-Herold M, Coelho-Filho OR, Blankstein R, Falk RH, Kwong RY. Quantification of extracellular matrix expansion by CMR in infiltrative heart disease. J Am Coll Cardiol Img. 2012;5(9):897–907. https://doi.org/10.1016/j.jcmg.2012.04.006.CrossRef

25.

Banypersad SM, Sado DM, Flett AS, Gibbs SD, Pinney JH, Maestrini V, et al. Quantification of myocardial extracellular volume fraction in systemic AL amyloidosis: an equilibrium contrast cardiovascular magnetic resonance study. Circ Cardiovasc Imaging. 2013;6(1):34–9. https://doi.org/10.1161/CIRCIMAGING.112.978627.PubMedCrossRef

26.

Fontana M, Banypersad SM, Treibel TA, Maestrini V, Sado DM, White SK, et al. Native T1 mapping in transthyretin amyloidosis. J Am Coll Cardiol Img. 2014;7(2):157–65. https://doi.org/10.1016/j.jcmg.2013.10.008.CrossRef

27.

Fontana M, White SK, Banypersad SM, Sado DM, Maestrini V, Flett AS, et al. Comparison of T1 mapping techniques for ECV quantification. Histological validation and reproducibility of ShMOLLI versus multibreath-hold T1 quantification equilibrium contrast CMR. J Cardiovasc Magn Reson. 2012;14:88. https://doi.org/10.1186/1532-429X-14-88.PubMedPubMedCentralCrossRef

28.

Perugini E, Guidalotti PL, Salvi F, Cooke RM, Pettinato C, Riva L, et al. Noninvasive etiologic diagnosis of cardiac amyloidosis using 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. J Am Coll Cardiol. 2005;46(6):1076–84. https://doi.org/10.1016/j.jacc.2005.05.073.PubMedCrossRef

29.

Bokhari S, Castano A, Pozniakoff T, Deslisle S, Latif F, Maurer MS. (99m)Tc-pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidoses. Circ Cardiovasc Imaging. 2013;6(2):195–201. https://doi.org/10.1161/CIRCIMAGING.112.000132.PubMedPubMedCentralCrossRef

30.

Rapezzi C, Quarta CC, Guidalotti PL, Pettinato C, Fanti S, Leone O, et al. Role of (99m)Tc-DPD scintigraphy in diagnosis and prognosis of hereditary transthyretin-related cardiac amyloidosis. J Am Coll Cardiol Img. 2011;4(6):659–70. https://doi.org/10.1016/j.jcmg.2011.03.016.CrossRef

31.

Castano A, Haq M, Narotsky DL, Goldsmith J, Weinberg RL, Morgenstern R, et al. Multicenter study of planar technetium 99m pyrophosphate cardiac imaging: predicting survival for patients with ATTR cardiac amyloidosis. JAMA Cardiol. 2016;1(8):880–9. https://doi.org/10.1001/jamacardio.2016.2839.PubMedCrossRef

32.

Aus dem Siepen F, Hein S, Bauer R, Katus HA, Kristen AV. Standard heart failure medication in cardiac transthyretin amyloidosis: useful or harmful? Amyloid. 2017;24(sup1):132–3. https://doi.org/10.1080/13506129.2016.1272453.PubMedCrossRef

33.

Ritts AJ, Cornell RF, Swiger K, Singh J, Goodman S, Lenihan DJ. Current concepts of cardiac amyloidosis: diagnosis, clinical management, and the need for collaboration. Heart Fail Clin. 2017;13(2):409–16. https://doi.org/10.1016/j.hfc.2016.12.003.PubMedCrossRef

34.

Falk RH. Diagnosis and management of the cardiac amyloidoses. Circulation. 2005;112(13):2047–60. https://doi.org/10.1161/CIRCULATIONAHA.104.489187.PubMedCrossRef

35.

Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):e147–239. https://doi.org/10.1016/j.jacc.2013.05.019.PubMedCrossRef

36.

Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Kardiol Pol. 2016;74(10):1037–147. https://doi.org/10.5603/KP.2016.0141.PubMedCrossRef

37.

Donnelly JP, Hanna M. Cardiac amyloidosis: an update on diagnosis and treatment. Cleve Clin J Med. 2017;84(12 Suppl 3):12–26. https://doi.org/10.3949/ccjm.84.s3.02.PubMedCrossRef

38.

Castano A, Drachman BM, Judge D, Maurer MS. Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs. Heart Fail Rev. 2015;20(2):163–78. https://doi.org/10.1007/s10741-014-9462-7.PubMedPubMedCentralCrossRef

39.

Muchtar E, Gertz MA, Kumar SK, Lin G, Boilson B, Clavell A, et al. Digoxin use in systemic light-chain (AL) amyloidosis: contra-indicated or cautious use? Amyloid. 2018;25(2):86–92. https://doi.org/10.1080/13506129.2018.1449744.PubMedCrossRef

40.

Longhi S, Quarta CC, Milandri A, Lorenzini M, Gagliardi C, Manuzzi L, et al. Atrial fibrillation in amyloidotic cardiomyopathy: prevalence, incidence, risk factors and prognostic role. Amyloid. 2015;22(3):147–55. https://doi.org/10.3109/13506129.2015.1028616.PubMedCrossRef

41.

Barbhaiya CR, Kumar S, Baldinger SH, Michaud GF, Stevenson WG, Falk R, et al. Electrophysiologic assessment of conduction abnormalities and atrial arrhythmias associated with amyloid cardiomyopathy. Heart Rhythm. 2016;13(2):383–90. https://doi.org/10.1016/j.hrthm.2015.09.016.PubMedCrossRef

42.

Mints YY, Doros G, Berk JL, Connors LH, Ruberg FL. Features of atrial fibrillation in wild-type transthyretin cardiac amyloidosis: a systematic review and clinical experience. ESC Heart Fail. 2018;5(5):772–9. https://doi.org/10.1002/ehf2.12308.PubMedPubMedCentralCrossRef

43.

Zhang H, El-Am EA, Thaden JJ, Pislaru SV, Scott CG, Krittanawong C, et al. Atrial fibrillation is not an independent predictor of outcome in patients with aortic stenosis. Heart. 2019. https://doi.org/10.1136/heartjnl-2019-314996.

44.

Martinez-Naharro A, Gonzalez-Lopez E, Corovic A, Mirelis JG, Baksi AJ, Moon JC, et al. High prevalence of intracardiac thrombi in cardiac amyloidosis. J Am Coll Cardiol. 2019;73(13):1733–4. https://doi.org/10.1016/j.jacc.2019.01.035.PubMedCrossRef

45.

Dubrey S, Pollak A, Skinner M, Falk RH. Atrial thrombi occurring during sinus rhythm in cardiac amyloidosis: evidence for atrial electromechanical dissociation. Br Heart J. 1995;74(5):541–4. https://doi.org/10.1136/hrt.74.5.541.PubMedPubMedCentralCrossRef

46.

Tan NY, Mohsin Y, Hodge DO, Lacy MQ, Packer DL, Dispenzieri A, et al. Catheter ablation for atrial arrhythmias in patients with cardiac amyloidosis. J Cardiovasc Electrophysiol. 2016;27(10):1167–73. https://doi.org/10.1111/jce.13046.PubMedCrossRef

47.

Rapezzi C, Merlini G, Quarta CC, Riva L, Longhi S, Leone O, et al. Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types. Circulation. 2009;120(13):1203–12. https://doi.org/10.1161/CIRCULATIONAHA.108.843334.PubMedCrossRef

48.•

. Yamamoto H, Yokochi T. Transthyretin cardiac amyloidosis: an update on diagnosis and treatment. ESC Heart Fail. 2019. https://doi.org/10.1002/ehf2.12518 Review of the new diagnostic methods for diagnosing CA.

49.

Kristen AV, Dengler TJ, Hegenbart U, Schonland SO, Goldschmidt H, Sack FU, et al. Prophylactic implantation of cardioverter-defibrillator in patients with severe cardiac amyloidosis and high risk for sudden cardiac death. Heart Rhythm. 2008;5(2):235–40. https://doi.org/10.1016/j.hrthm.2007.10.016.PubMedCrossRef

50.

Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: the Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J. 2015;36(41):2793–867. https://doi.org/10.1093/eurheartj/ehv316.PubMedCrossRef

51.

Donnellan E, Wazni OM, Saliba WI, Baranowski B, Hanna M, Martyn M, et al. Cardiac devices in patients with transthyretin amyloidosis: impact on functional class, left ventricular function, mitral regurgitation, and mortality. J Cardiovasc Electrophysiol. 2019;30(11):2427–32. https://doi.org/10.1111/jce.14180.PubMedCrossRef

52.

Estep JD, Bhimaraj A, Cordero-Reyes AM, Bruckner B, Loebe M, Torre-Amione G. Heart transplantation and end-stage cardiac amyloidosis: a review and approach to evaluation and management. Methodist DeBakey Cardiovasc J. 2012;8(3):8–16. https://doi.org/10.14797/mdcj-8-3-8.PubMedPubMedCentralCrossRef

53.

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. https://doi.org/10.1016/j.healun.2008.05.016.PubMedCrossRef

54.

Sousa M, Monohan G, Rajagopalan N, Grigorian A, Guglin M. Heart transplantation in cardiac amyloidosis. Heart Fail Rev. 2017;22(3):317–27. https://doi.org/10.1007/s10741-017-9601-z.PubMedCrossRef

55.

Bates M, Lieu D, Zagari M, Spiers A, Williamson T. A pharmacoeconomic evaluation of the use of dexrazoxane in preventing anthracycline-induced cardiotoxicity in patients with stage IIIB or IV metastatic breast cancer. Clin Ther. 1997;19(1):167–84.PubMedCrossRef

56.

Colvin M, Smith JM, Hadley N, Skeans MA, Carrico R, Uccellini K, et al. OPTN/SRTR 2016 annual data report: heart. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. 2018;18(Suppl 1):291–362. https://doi.org/10.1111/ajt.14561.CrossRef

57.

Holmgren G, Ericzon BG, Groth CG, Steen L, Suhr O, Andersen O, et al. Clinical improvement and amyloid regression after liver transplantation in hereditary transthyretin amyloidosis. Lancet. 1993;341(8853):1113–6. https://doi.org/10.1016/0140-6736(93)93127-m.PubMedCrossRef

58.

Kpodonu J, Massad MG, Caines A, Geha AS. Outcome of heart transplantation in patients with amyloid cardiomyopathy. J Heart Lung Transplant. 2005;24(11):1763–5. https://doi.org/10.1016/j.healun.2004.08.025.PubMedCrossRef

59.

Arpesella G, Chiappini B, Marinelli G, Mikus PM, Dozza F, Pierangeli A, et al. Combined heart and liver transplantation for familial amyloidotic polyneuropathy. J Thorac Cardiovasc Surg. 2003;125(5):1165–6. https://doi.org/10.1067/mtc.2003.151.PubMedCrossRef

60.

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. https://doi.org/10.1200/jco.2011.38.5724.PubMedPubMedCentralCrossRef

61.

Tandon N, Sidana S, Dispenzieri A, Gertz MA, Lacy MQ, Dingli D, et al. Impact of involved free light chain (FLC) levels in patients achieving normal FLC ratio after initial therapy in light chain amyloidosis (AL). Am J Hematol. 2018;93(1):17–22. https://doi.org/10.1002/ajh.24919.PubMedCrossRef

62.

Comenzo RL, Vosburgh E, Simms RW, Bergethon P, Sarnacki D, Finn K, et al. Dose-intensive melphalan with blood stem cell support for the treatment of AL amyloidosis: one-year follow-up in five patients. Blood. 1996;88(7):2801–6.PubMedCrossRef

63.

Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR, Kumar SK, Leung N, et al. Effect of hematologic response on outcome of patients undergoing transplantation for primary amyloidosis: importance of achieving a complete response. Haematologica. 2007;92(10):1415–8. https://doi.org/10.3324/haematol.11413.PubMedCrossRef

64.

Tsai SB, Seldin DC, Quillen K, Berk JL, Ruberg FL, Meier-Ewert H, et al. High-dose melphalan and stem cell transplantation for patients with AL amyloidosis: trends in treatment-related mortality over the past 17 years at a single referral center. Blood. 2012;120(22):4445–6. https://doi.org/10.1182/blood-2012-09-457341.PubMedCrossRef

65.

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. https://doi.org/10.1200/jco.2013.50.8499.PubMedPubMedCentralCrossRef

66.

Reece DE, Hegenbart U, Sanchorawala V, Merlini G, Palladini G, Blade J, et al. Efficacy and safety of once-weekly and twice-weekly bortezomib in patients with relapsed systemic AL amyloidosis: results of a phase 1/2 study. Blood. 2011;118(4):865–73. https://doi.org/10.1182/blood-2011-02-334227.PubMedCrossRef

67.

Mikhael JR, Schuster SR, Jimenez-Zepeda VH, Bello N, Spong J, Reeder CB, et al. Cyclophosphamide-bortezomib-dexamethasone (CyBorD) produces rapid and complete hematologic response in patients with AL amyloidosis. Blood. 2012;119(19):4391–4. https://doi.org/10.1182/blood-2011-11-390930.PubMedPubMedCentralCrossRef

68.

Venner CP, Lane T, Foard D, Rannigan L, Gibbs SD, Pinney JH, et al. Cyclophosphamide, bortezomib, and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression-free survival. Blood. 2012;119(19):4387–90. https://doi.org/10.1182/blood-2011-10-388462.PubMedCrossRef

69.

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(5):612–5. https://doi.org/10.1182/blood-2015-01-620302.PubMedCrossRef

70.

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(5):597–605. https://doi.org/10.1182/blood-2017-03-771220.PubMedPubMedCentralCrossRef

71.

Palladini G, Russo P, Lavatelli F, Nuvolone M, Albertini R, Bosoni T, et al. Treatment of patients with advanced cardiac AL amyloidosis with oral melphalan, dexamethasone, and thalidomide. Ann Hematol. 2009;88(4):347–50. https://doi.org/10.1007/s00277-008-0600-y.PubMedCrossRef

72.

Wechalekar AD, Goodman HJ, 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(2):457–64. https://doi.org/10.1182/blood-2006-07-035352.PubMedCrossRef

73.

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(10):1593–9. https://doi.org/10.3324/haematol.2013.084574.PubMedPubMedCentralCrossRef

74.

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(23):5397–404. https://doi.org/10.1182/blood-2012-02-413161.PubMedPubMedCentralCrossRef

75.•

Sher T, Fenton B, Akhtar A, Gertz MA. First report of safety and efficacy of daratumumab in 2 cases of advanced immunoglobulin light chain amyloidosis. Blood. 2016;128(15):1987–9. https://doi.org/10.1182/blood-2016-06-722496 Report of potential benefit of daratumumab in AL.PubMedCrossRef

76.

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(2):531–6. https://doi.org/10.1038/s41375-018-0262-2.PubMedCrossRef

77.

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. https://doi.org/10.1056/NEJMoa1504942.PubMedCrossRef

78.

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. https://doi.org/10.1200/jco.2015.63.6530.PubMedPubMedCentralCrossRef

79.

Hrncic R, Wall J, Wolfenbarger DA, Murphy CL, Schell M, Weiss DT, et al. Antibody-mediated resolution of light chain-associated amyloid deposits. Am J Pathol. 2000;157(4):1239–46. https://doi.org/10.1016/s0002-9440(10)64639-1.PubMedPubMedCentralCrossRef

80.

Solomon A, Weiss DT, Wall JS. Therapeutic potential of chimeric amyloid-reactive monoclonal antibody 11-1F4. Clin Cancer Res. 2003;9(10 Pt 2):3831s–8s.PubMed

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(sup1):58–9. https://doi.org/10.1080/13506129.2017.1292900.PubMedCrossRef

82.

Shames S, Goldsmith J, Maurer MS. Abstract 18-A-413-ASE, 29th Annual ASE. null. 2018.

83.

Stuckey A, Williams A, Richey T, Macy S, Wooliver C, Kennel S, et al. Preliminary pharmacokinetic study of a bispecific peptide for pretargeting immunotherapy of amyloidosis using PreClinical SPECT/CT. J Nucl Med. 2018;59(supplement 1):1834.

84.

Biolo A, Ramamurthy S, Connors LH, O’Hara CJ, Meier-Ewert HK, Soo Hoo PT, et al. Matrix metalloproteinases and their tissue inhibitors in cardiac amyloidosis: relationship to structural, functional myocardial changes and to light chain amyloid deposition. Circ Heart Fail. 2008;1(4):249–57.PubMedPubMedCentralCrossRef

85.

Wechalekar A, Whelan C. Encouraging impact of doxycycline on early mortality in cardiac light chain (AL) amyloidosis. Blood Cancer J. 2017;7(3):e546.PubMedPubMedCentralCrossRef

86.

Bulawa CE, Connelly S, DeVit M, Wang L, Weigel C, Fleming JA, et al. Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade. Proc Natl Acad Sci. 2012;109(24):9629–34.PubMedCrossRef

87.••

Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. New Engl J Med. 2018;379(11):1007–16 After this study, tafamidis was approved for the treatment of both wild-type and mutated TTR amyloid cardiomyopathy.PubMedCrossRef

88.

2019 FaD. 2019. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=211996. Accessed 09 Dec 2019

89.

Sekijima Y, Tojo K, Morita H, Koyama J, Ikeda S-i. Safety and efficacy of long-term diflunisal administration in hereditary transthyretin (ATTR) amyloidosis. Amyloid. 2015;22(2):79–83. https://doi.org/10.3109/13506129.2014.997872.PubMedCrossRef

90.

Castaño A, Helmke S, Alvarez J, Delisle S, Maurer MS. Diflunisal for ATTR cardiac amyloidosis. Congest Heart Fail. 2012;18(6):315–9.PubMedPubMedCentralCrossRef

91.

Ikram A, Donnelly JP, Sperry BW, Samaras C, Valent J, Hanna M. Diflunisal tolerability in transthyretin cardiac amyloidosis: a single center’s experience. Amyloid. 2018;25(3):197–202. https://doi.org/10.1080/13506129.2018.1519507.PubMedCrossRef

92.

Rosenblum H, Castano A, Alvarez J, Goldsmith J, Helmke S, Maurer MS. TTR (transthyretin) stabilizers are associated with improved survival in patients with TTR cardiac amyloidosis. Circ Heart Fail. 2018;11(4):e004769.PubMedPubMedCentralCrossRef

93.••

Ruberg FL, Grogan M, Hanna M, Kelly JW, Maurer MS. Transthyretin amyloid cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol. 2019;73(22):2872–91. https://doi.org/10.1016/j.jacc.2019.04.003 State-of-the-art-review of amyloidosis.PubMedCrossRef

94.

Penchala SC, Connelly S, Wang Y, Park MS, Zhao L, Baranczak A, et al. AG10 inhibits amyloidogenesis and cellular toxicity of the familial amyloid cardiomyopathy-associated V122I transthyretin. Proc Natl Acad Sci. 2013;110(24):9992–7. https://doi.org/10.1073/pnas.1300761110.PubMedCrossRef

95.

AG10 Phase II. http://ir.eidostx.com/news-releases/news-release-details/eidos-therapeutics-announces-positive-phase-2-data-ag10. Accessed 09 Dec 2019

96.

Sant’Anna R, Gallego P, Robinson LZ, Pereira-Henriques A, Ferreira N, Pinheiro F, et al. Repositioning tolcapone as a potent inhibitor of transthyretin amyloidogenesis and associated cellular toxicity. Nat Commun. 2016;7:10787.PubMedPubMedCentralCrossRef

97.

Coelho T, Adams D, Silva A, Lozeron P, Hawkins PN, Mant T, et al. Safety and efficacy of RNAi therapy for transthyretin amyloidosis. N Engl J Med. 2013;369(9):819–29.PubMedCrossRef

98.

Bumcrot D, Manoharan M, Koteliansky V, Sah DW. RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat Chem Biol. 2006;2(12):711–9.PubMedPubMedCentralCrossRef

99.

Butler JS, Chan A, Costelha S, Fishman S, Willoughby JL, Borland TD, et al. Preclinical evaluation of RNAi as a treatment for transthyretin-mediated amyloidosis. Amyloid. 2016;23(2):109–18.PubMedPubMedCentralCrossRef

100.••

Adams D, Gonzalez-Duarte A, O’Riordan WD, Yang C-C, Ueda M, Kristen AV, et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. New Engl J Med. 2018;379(1):11–21 This study led to the approval of patisiran for the treatment of adults with hereditary ATTR-related polyneuropathy.PubMedCrossRef

101.

Solomon SD, Adams D, Kristen A, Grogan M, González-Duarte A, Maurer MS, et al. Effects of patisiran, an RNA interference therapeutic, on cardiac parameters in patients with hereditary transthyretin-mediated amyloidosis: analysis of the APOLLO study. Circulation. 2019;139(4):431–43.PubMedCrossRef

102.••

Benson MD, Dasgupta NR, Rissing SM, Smith J, Feigenbaum H. Safety and efficacy of a TTR specific antisense oligonucleotide in patients with transthyretin amyloid cardiomyopathy. Amyloid. 2017;24(4):217–23 Following these results, inotersen has received FDA approval for patients with hereditary ATTR-related polyneuropathy.CrossRef

103.

Wu H, Lima WF, Zhang H, Fan A, Sun H, Crooke ST. Determination of the role of the human RNase H1 in the pharmacology of DNA-like antisense drugs. J Biol Chem. 2004;279(17):17181–9.PubMedCrossRef

104.

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(1):22–31.PubMedCrossRef

105.

Emdin M, Aimo A, Rapezzi C, Fontana M, Perfetto F, Seferović PM, et al. Treatment of cardiac transthyretin amyloidosis: an update. Eur Heart J. 2019;40(45):3699–706. https://doi.org/10.1093/eurheartj/ehz298.PubMedCrossRef

106.

Galant NJ, Bugyei-Twum A, Rakhit R, Walsh P, Sharpe S, Arslan PE, et al. Substoichiometric inhibition of transthyretin misfolding by immune-targeting sparsely populated misfolding intermediates: a potential diagnostic and therapeutic for TTR amyloidoses. Sci Rep. 2016;6:25080.PubMedPubMedCentralCrossRef

Title: Advances in the Treatment of Cardiac Amyloidosis
Authors: Ariane Vieira Scarlatelli Macedo, MD, MHS
Pedro Vellosa Schwartzmann, MD, PhD
Breno Moreno de Gusmão, MD, MHS
Marcelo Dantas Tavares de Melo, MD, PhD
Otávio Rizzi Coelho-Filho, MD, MPH, PhD
Publication date: 01-05-2020
Publisher: Springer US
Keywords: Cardiomyopathy
Heart Failure
Cardiac Amyloidosis
Amyloidosis
AL Amyloidosis
Published in: Current Treatment Options in Oncology / Issue 5/2020
Print ISSN: 1527-2729
Electronic ISSN: 1534-6277
DOI: https://doi.org/10.1007/s11864-020-00738-8

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Opinion statement

Please log in to get access to this content

Other articles of this Issue 5/2020

Current Treatment Options for Older Patients with Hodgkin Lymphoma

The Effect of Prognostic Communication on Patient Outcomes in Palliative Cancer Care: a Systematic Review

Donor-Transmitted Melanoma: Is It Still Bothering Us?

Human Colon Organoids and Other Laboratory Strategies to Enhance Patient Treatment Selection

Venous Thromboembolism Treatment and Prevention in Cancer Patients: Can We Use Pills Yet?

TRK Inhibitors in Non-Small Cell Lung Cancer

Keynote webinar | Spotlight on antibody–drug conjugates in cancer