Paolo Milani, Giampaolo Merlini, Giovanni Palladini
  • Paolo Milani
    Amyloidosis Research and Treatment Center, Foundation “Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo” and Department of Molecular Medicine, University of Pavia, Pavia, Italy, Italy
  • Giampaolo Merlini
    Amyloidosis Research and Treatment Center, Foundation “Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo” and Department of Molecular Medicine, University of Pavia, Pavia, Italy,
  • Giovanni Palladini
    Amyloidosis Research and Treatment Center, Foundation “Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo” and Department of Molecular Medicine, University of Pavia, Pavia, Italy, Italy |


Light chain (AL) amyloidosis is caused by a usually small plasma-cell clone that is able to produce the amyloidogenic lights chains. They are able to misfold and aggregate, deposit in tissues in the form of amyloid fibrils and lead to irreversible organ dysfunction and eventually death if treatment is late or ineffective. Cardiac damage is the most important prognostic determinant. The risk of dialysis is predicted by the severity of renal involvement, defined by the baseline proteinuria and glomerular filtration rate, and by response to therapy. The specific treatment is chemotherapy targeting the underlying plasma-cell clone. This needs be risk adapted, according to the severity of cardiac and/or multi-organ involvement. Autologous stem cell transplant (preceded by induction and/or followed by consolidation with bortezomib-based regimens) can be considered for low-risk patients (~20%). Bortezomib combined with alkylators is used in the majority of intermediate-risk patients, and with possible dose escalation in high-risk subjects. Novel, powerful anti-plasma cell agents were investigated in the relapsed/refractory setting, and are being moved to upfront therapy in clinical trials. In addition, the use of novel approaches based on antibodies targeting the amyloid deposits or small molecules interfering with the amyloidogenic process gave promising results in preliminary studies. Some of them are under evaluation in controlled trials. These molecules will probably add powerful complements to standard chemotherapy. The understanding of the specific molecular mechanisms of cardiac damage and the characteristics of the amyloidogenic clone are unveiling novel potential treatment approaches, moving towards a cure for this dreadful disease.

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Published: 2018-03-01 00:00:00
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Palladini G, Merlini G. What is new in diagnosis and management of light chain amyloidosis? Blood. 2016;128(2):159-168.

Merlini G, Stone M. Dangerous small B-cell clones. Blood. 2006;108(8):2520-2530.

Merlini G. AL amyloidosis: from molecular mechanisms to targeted therapies. Hematology Am Soc Hematol Educ Program. 2017;2017(1):1-12.

Wechalekar AD, Gillmore JD, Hawkins PN. Systemic amyloidosis. Lancet. 2016;387(10038):2641-2654.

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(15):2111-2119.

Bochtler T, Hegenbart U, Cremer F, et al. Evaluation of the cytogenetic aberration pattern in amyloid light chain amyloidosis as compared with monoclonal gammopathy of undetermined significance reveals common pathways of karyotypic instability. Blood. 2008;111(9):4700-4705.

Bochtler T, Hegenbart U, Kunz C, 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):1371-1378.

Muchtar E, Dispenzieri A, Kumar SK, 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):1562-1569.

Muchtar E, Dispenzieri A, Kumar SK, et al. Immunoparesis status in immunoglobulin light chain amyloidosis at diagnosis affects response and survival by regimen type. Haematologica. 2016;101(9):1102-1109.

Bochtler T, Hegenbart U, Kunz C, 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.

Bochtler T, Hegenbart U, Kunz C, 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.

Paiva B, Martinez-Lopez J, Corchete LA, et al. Phenotypic, transcriptomic, and genomic features of clonal plasma cells in light-chain amyloidosis. Blood. 2016;127(24):3035-3039.

da Silva Filho MI, Försti A, Weinhold N, et al. Genome-wide association study of immunoglobulin light chain amyloidosis in three patient cohorts: comparison with myeloma. Leukemia. 2017;31(8):1735-1742.

Sitia R, Palladini G, Merlini G. Bortezomib in the treatment of AL amyloidosis: targeted therapy? Haematologica. 2007;92(10):1302-1307.

Bianchi G, Oliva L, Cascio P, et al. The proteasome load versus capacity balance determines apoptotic sensitivity of multiple myeloma cells to proteasome inhibition. Blood. 2009;113(13):3040-3049.

Oliva L, Orfanelli U, Resnati M, et al. The amyloidogenic light chain is a stressor that sensitizes plasma cells to proteasome inhibitor toxicity. Blood. 2017;129(15):2132-2142.

Comenzo R, Zhang Y, Martinez C, Osman K, Herrera G. The tropism of organ involvement in primary systemic amyloidosis: contributions of Ig V(L) germ line gene use and clonal plasma cell burden. Blood. 2001;98(3):714-720.

Perfetti V, Casarini S, Palladini G, et al. Analysis of V(lambda)-J(lambda) expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r (lambdaIII) as a new amyloid-associated germline gene segment. Blood. 2002;100(3):948-953.

Abraham R, Geyer S, Price-Troska T, et al. Immunoglobulin light chain variable (V) region genes influence clinical presentation and outcome in light chain-associated amyloidosis (AL). Blood. 2003;101(10):3801-3808.

Kourelis TV, Dasari S, Theis JD, et al. Clarifying immunoglobulin gene usage in systemic and localized immunoglobulin light-chain amyloidosis by mass spectrometry. Blood. 2017;129(3):299-306.

Perfetti V, Palladini G, Casarini S, et al. The repertoire of λ light chains causing predominant amyloid heart involvement and identification of a preferentially involved germline gene, IGLV1-44. Blood. 2012;119(1):144-150.

Palladini G, Campana C, Klersy C, et al. Serum N-terminal pro-brain natriuretic peptide is a sensitive marker of myocardial dysfunction in AL amyloidosis. Circulation. 2003;107(19):2440-2445.

Palladini G, Lavatelli F, Russo P, et al. Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL. Blood. 2006;107(10):3854-3858.

Palladini G, Barassi A, Klersy C, et al. The combination of high-sensitivity cardiac troponin T (hs-cTnT) at presentation and changes in N-terminal natriuretic peptide type B (NT-proBNP) after chemotherapy best predicts survival in AL amyloidosis. Blood. 2010;116(18):3426-3430.

Liao R, Jain M, Teller P, et al. Infusion of light chains from patients with cardiac amyloidosis causes diastolic dysfunction in isolated mouse hearts. Circulation. 2001;104(14):1594-1597.

Diomede L, Rognoni P, Lavatelli F, et al. A Caenorhabditis elegans-based assay recognizes immunoglobulin light chains causing heart amyloidosis. Blood. 2014;123(23):3543-3552.

Mishra S, Guan J, Plovie E, et al. Human amyloidogenic light chain proteins result in cardiac dysfunction, cell death, and early mortality in zebrafish. Am J Physiol Heart Circ Physiol. 2013;305(1):H95-103.

Lavatelli F, Imperlini E, Orru S, et al. Novel mitochondrial protein interactors of immunoglobulin light chains causing heart amyloidosis. FASEB J. 2015;29(11):4614-4628.

Oberti L, Rognoni P, Barbiroli A, et al. Concurrent structural and biophysical traits link with immunoglobulin light chains amyloid propensity. Sci Rep. 2017;7(1):16809.

Perlini S, Salinaro F, Musca F, et al. Prognostic value of depressed midwall systolic function in cardiac light-chain amyloidosis. J Hypertens. 2014;32(5):1121-1131; discussion 1131.

Buss SJ, Emami M, Mereles D, et al. Longitudinal left ventricular function for prediction of survival in systemic light-chain amyloidosis: incremental value compared with clinical and biochemical markers. J Am Coll Cardiol. 2012;60(12):1067-1076.

Fontana M, Chung R, Hawkins PN, Moon JC. Cardiovascular magnetic resonance for amyloidosis. Heart Fail Rev. 2015;20(2):133-144.

Park MA, Padera RF, Belanger A, et al. 18F-Florbetapir Binds Specifically to Myocardial Light Chain and Transthyretin Amyloid Deposits: Autoradiography Study. Circ Cardiovasc Imaging. 2015;8(8).

Gillmore JD, Maurer MS, Falk RH, et al. Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation. 2016;133(24):2404-2412.

Merlini G, Palladini G. Differential diagnosis of monoclonal gammopathy of undetermined significance. Hematology Am Soc Hematol Educ Program. 2012;2012:595-603.

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(10):920-928.

Kourelis TV, Kumar SK, Go RS, et al. Immunoglobulin light chain amyloidosis is diagnosed late in patients with preexisting plasma cell dyscrasias. Am J Hematol. 2014;89(11):1051-1054.

Merlini G, Wechalekar AD, Palladini G. Systemic light chain amyloidosis: an update for treating physicians. Blood. 2013;121(26):5124-5130.

Foli A, Palladini G, Caporali R, et al. The role of minor salivary gland biopsy in the diagnosis of systemic amyloidosis: results of a prospective study in 62 patients. Amyloid. 2011;18 Suppl 1:80-82.

Fernandez de Larrea C, Verga L, Morbini P, et al. A practical approach to the diagnosis of systemic amyloidoses. Blood. 2015;125(14):2239-2244.

Muchtar E, Dispenzieri A, Lacy MQ, et al. Overuse of organ biopsies in immunoglobulin light chain amyloidosis (AL): the consequence of failure of early recognition. Ann Med. 2017;49(7):545-551.

Anesi E, Palladini G, Perfetti V, Arbustini E, Obici L, Merlini G. Therapeutic advances demand accurate typing of amyloid deposits. Am J Med. 2001;111(3):243-244.

Lachmann H, Booth D, Booth S, et al. Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med. 2002;346(23):1786-1791.

Comenzo R, Zhou P, Fleisher M, Clark B, Teruya-Feldstein J. Seeking confidence in the diagnosis of systemic AL (Ig light-chain) amyloidosis: patients can have both monoclonal gammopathies and hereditary amyloid proteins. Blood. 2006;107(9):3489-3491.

Satoskar A, Burdge K, Cowden D, Nadasdy G, Hebert L, Nadasdy T. Typing of amyloidosis in renal biopsies: diagnostic pitfalls. Arch Pathol Lab Med. 2007;131(6):917-922.

Satoskar AA, Efebera Y, Hasan A, et al. Strong transthyretin immunostaining: potential pitfall in cardiac amyloid typing. Am J Surg Pathol. 2011;35(11):1685-1690.

Schönland SO, Hegenbart U, Bochtler T, et al. Immunohistochemistry in the classification of systemic forms of amyloidosis: a systematic investigation of 117 patients. Blood. 2012;119(2):488-493.

Vrana J, Gamez J, Madden B, Theis J, Bergen Hr, Dogan A. Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens. Blood. 2009;114(24):4957-4959.

Brambilla F, Lavatelli F, Di Silvestre D, et al. Reliable typing of systemic amyloidoses through proteomic analysis of subcutaneous adipose tissue. Blood. 2012;119(8):1844-1847.

Katzmann J, Kyle R, Benson J, et al. Screening panels for detection of monoclonal gammopathies. Clin Chem. 2009;55(8):1517-1522.

Bochtler T, Hegenbart U, Heiss C, et al. Evaluation of the serum-free light chain test in untreated patients with AL amyloidosis. Haematologica. 2008;93(3):459-462.

Palladini G, Russo P, Bosoni T, et al. Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. Clin Chem. 2009;55(3):499-504.

Palladini G, Jaccard A, Milani P, et al. Circulating free light chain measurement in the diagnosis, prognostic assessment and evaluation of response of AL amyloidosis: comparison of Freelite and N latex FLC assays. Clin Chem Lab Med. 2017.

Dispenzieri A, Gertz M, Kyle R, et al. Serum cardiac troponins and N-terminal pro-brain natriuretic peptide: a staging system for primary systemic amyloidosis. J Clin Oncol. 2004;22(18):3751-3757.

Wechalekar AD, Schonland SO, Kastritis E, et al. A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. Blood. 2013;121(17):3420-3427.

Kourelis TV, Kumar SK, Gertz MA, 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):4319-4324.

Dittrich T, Bochtler T, Kimmich C, et al. AL amyloidosis patients with low amyloidogenic free light chain levels at first diagnosis have an excellent prognosis. Blood. 2017;130(5):632-642.

Milani P, Basset M, Russo F, Foli A, Merlini G, Palladini G. Patients with light-chain amyloidosis and low free light-chain burden have distinct clinical features and outcome. Blood. 2017;130(5):625-631.

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(9):989-995.

Palladini G, Hegenbart U, Milani P, et al. A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis. Blood. 2014;124(15):2325-2332.

D'Souza A, Dispenzieri A, Wirk 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(32):3741-3749.

Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-e548.

Dispenzieri A, Seenithamby K, Lacy MQ, et al. Patients with immunoglobulin light chain amyloidosis undergoing autologous stem cell transplantation have superior outcomes compared with patients with multiple myeloma: a retrospective review from a tertiary referral center. Bone Marrow Transplant. 2013;48(10):1302-1307.

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(36):4541-4549.

Merlini G, Lousada I, Ando Y, 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(10):1979-1986.

Sidana S, Tandon, N., Dispenzieri, A., Gertz, M. A., Buadi, F. K., Lacy, M. Q., Dingli, D., Fonder, A., Hayman, S. R., Hobbs, M., Gonsalves, W. I., Hwa, Y. L., Kapoor, P., Kyle, R. A., Leung, N., Go, R. S., Lust, J. A., Russell, S. J., Zeldenrust, S. R., Binder, M., Rajkumar, S. V., & Kumar, S. K. Composite Organ and Hematologic Response Model Risk Stratifies Patients with Light Chain Amyloidosis. . Blood. 2017;130(Suppl 1), 3046.

Muchtar E, Dispenzieri, A., Lacy, M. Q., Leung, N., Buadi, F. K., Grogan, M., Hayman, S. R., Kapoor, P., Hwa, Y. L., Fonder, A., Hobbs, M., Chakraborty, R., Gonsalves, W. I., Kourelis, T., Warsame, R., Russell, S. J., Lust, J. A., Lin, Y., Go, R. S., Zeldenrust, S., Kyle, R. A., Rajkumar, S. V., Kumar, S. K., & Gertz, M. A. . Depth of Organ Response in Newly Diagnosed AL Amyloidosis Is Associated with Improved Survival: Improved Outcome Discrimination with Graded Organ Response. . Blood. 2017;130(Suppl 1), 3154.

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):2345-2347.

Gertz MA, Lacy MQ, Dispenzieri A, et al. Refinement in patient selection to reduce treatment-related mortality from autologous stem cell transplantation in amyloidosis. Bone Marrow Transplant. 2013;48(4):557-561.

Dispenzieri A, Buadi F, Kumar SK, et al. Treatment of Immunoglobulin Light Chain Amyloidosis: Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Statement. Mayo Clin Proc. 2015;90(8):1054-1081.

Cibeira MT, Sanchorawala V, Seldin DC, et al. Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation: long-term results in a series of 421 patients. Blood. 2011;118(16):4346-4352.

Landau H, Smith M, Landry C, et al. Long-term event-free and overall survival after risk-adapted melphalan and SCT for systemic light chain amyloidosis. Leukemia. 2017;31(1):136-142.

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(10):984-988.

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(8):2936-2938.

Palladini G, Russo P, Nuvolone M, et al. Treatment with oral melphalan plus dexamethasone produces long-term remissions in AL amyloidosis. Blood. 2007;110(2):787-788.

Palladini G, Milani P, Foli A, 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):743-750.

Jaccard A, Moreau P, Leblond V, et al. High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. N Engl J Med. 2007;357(11):1083-1093.

Kastritis E, Wechalekar A, Dimopoulos M, et al. Bortezomib with or without dexamethasone in primary systemic (light chain) amyloidosis. J Clin Oncol. 2010;28(6):1031-1037.

Reece D, Sanchorawala V, Hegenbart U, et al. Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis: results of a phase 1 dose-escalation study. Blood. 2009;114(8):1489-1497.

Reece DE, Hegenbart U, Sanchorawala V, 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):865-873.

Reece DE, Hegenbart U, Sanchorawala V, et al. Long-term follow-up from a phase 1/2 study of single-agent bortezomib in relapsed systemic AL amyloidosis. Blood. 2014;124(16):2498-2506.

Palladini G, Sachchithanantham S, Milani P, et al. A European collaborative study of cyclophosphamide, bortezomib, and dexamethasone in upfront treatment of systemic AL amyloidosis. Blood. 2015;126(5):612-615.

Palladini G, Milani P, Foli A, 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(12):2311-2316.

Venner CP, Gillmore JD, Sachchithanantham S, et al. A matched comparison of cyclophosphamide, bortezomib and dexamethasone (CVD) versus risk-adapted cyclophosphamide, thalidomide and dexamethasone (CTD) in AL amyloidosis. Leukemia. 2014;28(12):2304-2310.

Kastritis E, Leleu X, Arnulf B, 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).

Kastritis E, Gavriatopoulou M, Roussou 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(6):e570.

Sidana S, Tandon N, Gertz MA, et al. Impact of prior melphalan exposure on stem cell collection in light chain amyloidosis. Bone Marrow Transplant. 2017.

Palladini G, Milani P, Merlini G. Novel strategies for the diagnosis and treatment of cardiac amyloidosis. Expert review of cardiovascular therapy. 2015;13(11):1195-1211.

Manwani R, Foard D, Mahmood S, et al. Rapid hematological responses improve outcomes in patients with very advanced (Stage IIIb) cardiac immunoglobulin light chain amyloidosis. Haematologica. 2018.

Palladini G, Milani P, Foli A, et al. Presentation and outcome with second line treatment in AL amyloidosis previously sensitive to non-transplant therapies. Blood. 2017.

Milani P, Gertz MA, Merlini G, Dispenzieri A. Attitudes about when and how to treat patients with AL amyloidosis: an international survey. Amyloid. 2017:1-4.

Tandon N, Sidana S, Gertz MA, et al. Treatment Patterns and Outcome Following Initial Relapse or Refractory Disease in Patients with Systemic Light Chain Amyloidosis. Am J Hematol. 2017.

Manwani R, Hegenbart, U., Foard, D., Mahmood, S., Sachchithanantham, S., Yong, K., Popat, R., Kyriakou, C., Rabin, N., Fontana, M., Whelan, C., Lachmann, H., Lane, T., Quarta, C., Gillmore, J., Dittrich, T., Kimmich, C., Hawkins, P., Schönland, S., & Wechalekar, A. D. Safety and Efficacy of Deferred Autologous Stem Cell Transplantation in Patients with Systemic AL Amyloidosis with Significant Cardiac Involvement at Presentation. Blood. 2017;130(Suppl 1), 1815.

Dispenzieri A, Lacy M, Zeldenrust S, et al. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood. 2007;109(2):465-470.

Sanchorawala V, Wright D, Rosenzweig M, et al. Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial. Blood. 2007;109(2):492-496.

Palladini G, Russo P, Foli A, et al. Salvage therapy with lenalidomide and dexamethasone in patients with advanced AL amyloidosis refractory to melphalan, bortezomib, and thalidomide. Ann Hematol. 2011.

Kastritis E, Terpos E, Roussou M, 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):5384-5390.

Kumar SK, Hayman SR, Buadi FK, et al. Lenalidomide, cyclophosphamide, and dexamethasone (CRd) for light-chain amyloidosis: long-term results from a phase 2 trial. Blood. 2012;119(21):4860-4867.

Mahmood S, Venner CP, Sachchithanantham S, et al. Lenalidomide and dexamethasone for systemic AL amyloidosis following prior treatment with thalidomide or bortezomib regimens. Br J Haematol. 2014;166(6):842-848.

Specter R, Sanchorawala V, Seldin DC, et al. Kidney dysfunction during lenalidomide treatment for AL amyloidosis. Nephrol Dial Transplant. 2011;26(3):881-886.

Moreau P, Jaccard A, Benboubker L, et al. Lenalidomide in combination with melphalan and dexamethasone in patients with newly diagnosed AL amyloidosis: a multicenter phase 1/2 dose-escalation study. Blood. 2010;116(23):4777-4782.

Sanchorawala V, Patel JM, Sloan JM, Shelton AC, Zeldis JB, Seldin DC. Melphalan, lenalidomide and dexamethasone for the treatment of immunoglobulin light chain amyloidosis: results of a phase II trial. Haematologica. 2013;98(5):789-792.

Cibeira MT, Oriol A, Lahuerta JJ, et al. A phase II trial of lenalidomide, dexamethasone and cyclophosphamide for newly diagnosed patients with systemic immunoglobulin light chain amyloidosis. Br J Haematol. 2015;170(6):804-813.

Hegenbart U, Bochtler T, Benner A, 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(8):1424-1431.

Dispenzieri A, Buadi F, Laumann K, et al. Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. Blood. 2012;119(23):5397-5404.

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):1059-1062.

Palladini G, Milani P, Foli A, et al. A phase 2 trial of pomalidomide and dexamethasone rescue treatment in patients with AL amyloidosis. Blood. 2017;129(15):2120-2123.

Warsame R, Laplant, B., Laumann, K., Kumar, S. K., Gertz, M. A., Kyle, R. A., Lacy, M. Q., Dingli, D., Leung, N., Buadi, F. K., Hayman, S. R., Kapoor, P., Hwa, Y. L., Fonder, A., Hobbs, M., Gonsalves, W. I., Kourelis, T., Russell, S. J., Zeldenrust, S., Lin, Y., Muchtar, E., Go, R. S., Rajkumar, S. V., & Dispenzieri, A. . Long-Term Outcomes of IMiD Based Trials in Patients with Immunoglobulin Light Chain Amyloidosis (AL): A Pooled Analysis. Blood. 2017;130(Suppl 1), 1833.

Cohen A, Landau H, Scott E, et al. Safety and Efficacy of Carfilzomib (CFZ) in Previously-Treated Systemic Light-Chain (AL) Amyloidosis. Blood. 2016;128(22).

Sanchorawala V, Palladini G, Kukreti V, 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.

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.

Sanchorawala V, Sarosiek, S., Sloan, J. M., Brauneis, D., Migre, M. E., Mistark, M., Santos, S., Fennessey, S., & Shelton, A. C. . Safety and Tolerability of Daratumumab in Patients with Relapsed Light Chain (AL) Amyloidosis: Preliminary Results of a Phase II Study. Blood. 2017;130(Suppl 1), 507.

Roussel M, Stoppa, A., Perrot, A., Karlin, L., Arnulf, B., Macro, M., Huart, A., Frenzel, L., Morel, P., Boyle, E., Dorvaux, V., Merlini, G., Palladini, G., Lavergne, D., Bridoux, F., & Jaccard, A. A Prospective Phase II of Daratumumab in Previously-Treated Systemic Light-Chain (AL) Amyloidosis. Blood. 2017;130(Suppl 1), 508.

Merlini G, Ascari E, Amboldi N, et al. Interaction of the anthracycline 4'-iodo-4'-deoxydoxorubicin with amyloid fibrils: inhibition of amyloidogenesis. Proc Natl Acad Sci U S A. 1995;92(7):2959-2963.

Merlini G, Anesi E, Garini P, et al. Treatment of AL amyloidosis with 4'-lodo-4'-deoxydoxorubicin: an update. Blood. 1999;93(3):1112-1113.

Palha JA, Ballinari D, Amboldi N, et al. 4'-Iodo-4'-deoxydoxorubicin disrupts the fibrillar structure of transthyretin amyloid. Am J Pathol. 2000;156(6):1919-1925.

Cardoso I, Merlini G, Saraiva MJ. 4'-iodo-4'-deoxydoxorubicin and tetracyclines disrupt transthyretin amyloid fibrils in vitro producing noncytotoxic species: screening for TTR fibril disrupters. FASEB J. 2003;17(8):803-809.

Gertz M, Lacy M, Dispenzieri A, et al. A multicenter phase II trial of 4'-iodo-4'deoxydoxorubicin (IDOX) in primary amyloidosis (AL). Amyloid. 2002;9(1):24-30.

Cardoso I, Saraiva MJ. Doxycycline disrupts transthyretin amyloid: evidence from studies in a FAP transgenic mice model. FASEB J. 2006;20(2):234-239.

Ward JE, Ren R, Toraldo G, et al. Doxycycline reduces fibril formation in a transgenic mouse model of AL amyloidosis. Blood. 2011;118(25):6610-6617.

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

Ehrnhoefer DE, Bieschke J, Boeddrich A, et al. EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers. Nat Struct Mol Biol. 2008;15(6):558-566.

Hora M, Carballo-Pacheco M, Weber B, et al. Epigallocatechin-3-gallate preferentially induces aggregation of amyloidogenic immunoglobulin light chains. Sci Rep. 2017;7:41515.

Hunstein W. Epigallocathechin-3-gallate in AL amyloidosis: a new therapeutic option? Blood. 2007;110(6):2216.

Mereles D, Buss SJ, Hardt SE, Hunstein W, Katus HA. Effects of the main green tea polyphenol epigallocatechin-3-gallate on cardiac involvement in patients with AL amyloidosis. Clin Res Cardiol. 2010;99(8):483-490.

Meshitsuka S, Shingaki S, Hotta M, et al. Phase 2 trial of daily, oral epigallocatechin gallate in patients with light-chain amyloidosis. Int J Hematol. 2017;105(3):295-308.

Pepys M, Herbert J, Hutchinson W, et al. Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature. 2002;417(6886):254-259.

Gillmore JD, Tennent GA, Hutchinson WL, et al. Sustained pharmacological depletion of serum amyloid P component in patients with systemic amyloidosis. Br J Haematol. 2010;148(5):760-767.

Richards DB, Cookson LM, Berges AC, et al. Therapeutic Clearance of Amyloid by Antibodies to Serum Amyloid P Component. N Engl J Med. 2015;373(12):1106-1114.

Edwards CV, Gould J, Langer AL, 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):58-59.

Edwards CV, Gould, J., Langer, A. L., Mapara, M. Y., Radhakrishnan, J., Maurer, M. S., Raza, S., Mears, J. G., Leng, S., Wall, J. S., Eisenberger, A., Solomon, A., & Lentzsch, S. Final Analysis of the Phase 1a/b Study of Chimeric Fibril-Reactive Monoclonal Antibody 11-1F4 in Patients with Relapsed or Refractory AL Amyloidosis. Blood. 2017;130(Suppl 1), 509.

Gertz MA, Landau H, Comenzo RL, 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):1097-1103.


Bernardi L, Passino C, Porta C, Anesi E, Palladini G, Merlini G. Widespread cardiovascular autonomic dysfunction in primary amyloidosis: does spontaneous hyperventilation have a compensatory role against postural hypotension? Heart. 2002;88(6):615-621.

Caccialanza R, Palladini G, Klersy C, et al. Nutritional status of outpatients with systemic immunoglobulin light-chain amyloidosis. American Journal of Clinical Nutrition. 2006;83(2):350-354.

Caccialanza R, Palladini G, Klersy C, et al. Nutritional status independently affects quality of life of patients with systemic immunoglobulin light-chain (AL) amyloidosis. Ann Hematol. 2012;91(3):399-406.

Caccialanza R, Palladini G, Klersy C, et al. Malnutrition at diagnosis predicts mortality in patients with systemic immunoglobulin light-chain amyloidosis independently of cardiac stage and response to treatment. JPEN J Parenter Enteral Nutr. 2014;38(7):891-894.

Caccialanza R, Palladini G, Cereda E, et al. Nutritional counseling improves quality of life and preserves body weight in systemic immunoglobulin light-chain (AL) amyloidosis. Nutrition. 2015;31(10):1228-1234.

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(9):989-995.

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