系统性免疫球蛋白轻链型淀粉样变性的治疗进展

doi:10.35541/cjd.20180845

中华皮肤科杂志 ›› 2020, Vol. 53 ›› Issue (8): 668-672.doi: 10.35541/cjd.20180845

• 综述 • 上一篇

系统性免疫球蛋白轻链型淀粉样变性的治疗进展

付玉娟周炯郑敏

浙江大学医学院附属第二医院皮肤科，杭州 310000

收稿日期:2018-10-29 修回日期:2019-05-25 发布日期:2020-07-31
通讯作者: 郑敏 E-mail:minz@zju.edu.cn

Treatment of systemic immunoglobulin light chain amyloidosis

Fu Yujuan, Zhou Jiong, Zheng Min#br#

#br#

Department of Dermatology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, China

Received:2018-10-29 Revised:2019-05-25 Published:2020-07-31
Contact: Zheng Min E-mail:minz@zju.edu.cn

摘要/Abstract

摘要： 【摘要】系统性免疫球蛋白轻链型淀粉样变性是因淀粉样蛋白原纤维聚集沉积引起的蛋白质错误折叠疾病，可导致器官不可逆性功能障碍。本文根据疾病危险分层详述本病的系统性治疗方法，低危系统性免疫球蛋白轻链型淀粉样变性患者适用化疗结合自体造血干细胞移植，中高危患者可用蛋白酶抑制剂如硼替佐米、卡非佐米及依沙唑米和免疫调节药物如来那度胺、泊马度胺及新型免疫制剂如达拉图马布、NEOD001等治疗。

关键词: 淀粉样变性, 免疫球蛋白轻链, 临床方案

Abstract: 【Abstract】 Systemic immunoglobulin light chain amyloidosis is a protein misfolding disease caused by the? highly organized amyloid fibrillar aggregates that lead to irreversible organ dysfunction. This review summarizes systemic therapies for this disease according to the disease risk stratification. Patients with low-risk systemic immunoglobulin light chain amyloidosis are eligible for chemotherapy combined with autologous hematopoietic stem cell transplantation. Patients with high-risk systemic immunoglobulin light chain amyloidosis can be treated with protease inhibitors (such as bortezomib, carfilzomib and ixazomib), immunomodulatory agents (such as lenalidomide, pomalidomide) and new immunological agents (such as daratumumab and NEOD001).

Key words: Amyloidosis, Immunoglobulin light chains, Clinical protocols

付玉娟周炯郑敏. 系统性免疫球蛋白轻链型淀粉样变性的治疗进展[J]. 中华皮肤科杂志, 2020,53(8):668-672. doi:10.35541/cjd.20180845

Fu Yujuan, Zhou Jiong, Zheng Min. Treatment of systemic immunoglobulin light chain amyloidosis[J]. Chinese Journal of Dermatology, 2020, 53(8): 668-672.doi:10.35541/cjd.20180845

参考文献 46

［1］	Quock TP, Yan T, Chang E, et al. Healthcare resource utilization and costs in amyloid light⁃chain amyloidosis: a real⁃world study using US claims data［J］. J Comp Eff Res, 2018,7（6）:549⁃559. doi: 10.2217/cer⁃2017⁃0100.
［2］	Quock TP, Yan T, Chang E, et al. Epidemiology of AL amyloidosis: a real⁃world study using US claims data［J］. Blood Adv, 2018,2（10）:1046⁃1053. doi: 10.1182/bloodadvances.2018 016402.
［3］	Lousada I, Comenzo RL, Landau H, et al. Light chain amyloidosis: patient experience survey from the amyloidosis research consortium［J］. Adv Ther, 2015,32（10）:920⁃928. doi: 10.1007/s12325⁃015⁃0250⁃0.
［4］	Andrei M, Wang JC. Cutaneous light chain amyloidosis with multiple myeloma: a concise review［J］. Hematol Oncol Stem Cell Ther, 2018, pii:S1658⁃3876（18）30095⁃5. doi: 10.1016/j.hemonc.2018.09.003.
［5］	Wanat KA, Kim B, Rosenbach M. Multisystem diseases affecting the skin and eye［J］. Clin Dermatol, 2016,34（2）:214⁃241. doi: 10.1016/j.clindermatol.2015.11.013.
［6］	Mahmood S, Bridoux F, Venner CP, et al. Natural history and outcomes in localised immunoglobulin light⁃chain amyloidosis: a long⁃term observational study［J］. Lancet Haematol, 2015,2（6）:e241⁃e250. doi: 10.1016/S2352⁃3026（15）00068⁃X.
［7］	Dispenzieri A, Gertz MA, Kyle RA, et al. Serum cardiac troponins and N⁃terminal pro⁃brain natriuretic peptide: a staging system for primary systemic amyloidosis［J］. J Clin Oncol, 2004,22（18）:3751⁃3757. doi: 10.1200/JCO.2004.03.029.
［8］	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］. J Clin Oncol, 2012,30（36）:4541⁃4549. doi: 10.1200/JCO.2011.37.7614.
［9］	Sidiqi MH, Aljama MA, Jevremovic D, et al. Prognostic significance of stringent complete response after stem cell transplantation in immunoglobulin light chain amyloidosis［J］. Biol Blood Marrow Transplant, 2018,24（11）:2360⁃2364. doi: 10.1016/j.bbmt.2018.06.027.
［10］	Nguyen VP, Landau H, Quillen K, et al. Modified high⁃dose melphalan and autologous stem cell transplantation for immunoglobulin light chain amyloidosis［J］. Biol Blood Marrow Transplant, 2018,24（9）:1823⁃1827. doi: 10.1016/j.bbmt.2018.06. 018.
［11］	Afrough A, Saliba RM, Hamdi A, et al. Impact of induction therapy on the outcome of immunoglobulin light chain amyloidosis after autologous hematopoietic stem cell transplantation［J］. Biol Blood Marrow Transplant, 2018,24（11）:2197⁃2203. doi: 10.1016/j.bbmt.2018.07.010.
［12］	Merlini G. AL amyloidosis: from molecular mechanisms to targeted therapies［J］. Hematology Am Soc Hematol Educ Program, 2017,2017（1）:1⁃12. doi: 10.1182/asheducation⁃2017. 1.1.
［13］	Kumar SK, Dispenzieri A, Lacy MQ, et al. Doxycycline used as post transplant antibacterial prophylaxis improves survival in patients with light chain amyloidosis undergoing autologous stem cell transplantation［J］. Blood, 2012,120（21）:3138.
［14］	Wechalekar AD, Whelan C. Encouraging impact of doxycycline on early mortality in cardiac light chain （AL） amyloidosis［J］. Blood Cancer J, 2017,7（3）:e546. doi: 10.1038/bcj.2017.26.
［15］	Sher T,Gertz MA. Stem cell transplantation for immunoglobulin light chain amyloidosis［J］. Curr Probl Cancer, 2017,41（2）:129⁃137. doi: 10.1016/j.currproblcancer.2017.03.001.
［16］	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［J］. Leukemia, 2017,31（1）:136⁃142. doi: 10.1038/leu.2016.229.
［17］	Browning S, Quillen K, Sloan JM, et al. Hematologic relapse in AL amyloidosis after high⁃dose melphalan and stem cell transplantation［J］. Blood, 2017,130（11）:1383⁃1386. doi: 10. 1182/blood⁃2017⁃06⁃788729.
［18］	Warsame R, Bang SM, Kumar SK, et al. Outcomes and treatments of patients with immunoglobulin light chain amyloidosis who progress or relapse postautologous stem cell transplant［J］. Eur J Haematol, 2014,92（6）:485⁃490. doi: 10.1111/ejh.12282.
［19］	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［J］. Haematologica, 2014,99（4）:743⁃750. doi: 10.3324/haematol. 2013.095463.
［20］	Kastritis E, Leleu X, Arnulf B, et al. A randomized phaseⅢ trial of Melphalan and Dexamethasone （MDex） versus Bortezomib, Melphalan and Dexamethasone （BMDex） for untreated patients with AL amyloidosis［J］. Blood, 2016,128（22）:646.
［21］	Mikhael JR, Schuster SR, Jimenez⁃Zepeda VH, et al. Cyclophosphamide⁃bortezomib⁃dexamethasone （CyBorD） produces rapid and complete hematologic response in patients with AL amyloidosis［J］. Blood, 2012,119（19）:4391⁃4394. doi: 10.1182/blood⁃2011⁃11⁃390930.
［22］	Venner CP, Lane T, Foard D, et al. Cyclophosphamide, bortezomib, and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression⁃free survival［J］. Blood, 2012,119（19）:4387⁃4390. doi: 10.1182/blood⁃2011⁃10⁃388462.
［23］	Palladini G, Sachchithanantham S, Milani P, et al. A European collaborative study of cyclophosphamide, bortezomib, and dexamethasone in upfront treatment of systemic AL amyloidosis［J］. Blood, 2015,126（5）:612⁃615. doi: 10.1182/blood⁃2015⁃01⁃620302.
［24］	Jaccard A, Comenzo RL, Hari P, et al. Efficacy of bortezomib, cyclophosphamide and dexamethasone in treatment⁃naïve patients with high⁃risk cardiac AL amyloidosis （Mayo Clinic stageⅢ）［J］. Haematologica, 2014,99（9）:1479⁃1485. doi: 10. 3324/haematol.2014.104109.
［25］	Le BF, Molinier⁃Frenkel V, Guellich A, et al. Sequential cyclophosphamide⁃bortezomib⁃dexamethasone unmasks the harmful cardiac effect of dexamethasone in primary light⁃chain cardiac amyloidosis［J］. Eur J Cancer, 2017,76:183⁃187. doi: 10.1016/j.ejca.2017.02.004.
［26］	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［J］. Blood Cancer J, 2017,7（6）:e570. doi: 10.1038/bcj.2017.47.
［27］	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［J］. Blood, 2016,128（4）:594⁃602. doi: 10.1182/blood⁃2015⁃10⁃676361.
［28］	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］. J Clin Oncol, 2015,33（12）:1371⁃1378. doi: 10.1200/JCO.2014.57.4947.
［29］	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［J］. Haematologica, 2017,102（8）:1424⁃1431. doi: 10.3324/haematol.2016.163246.
［30］	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［J］. Am J Hematol, 2017,92（6）:549⁃554. doi: 10.1002/ajh.24723.
［31］	Mahmood S, Venner CP, Sachchithanantham S, et al. Lenalidomide and dexamethasone for systemic AL amyloidosis following prior treatment with thalidomide or bortezomib regimens［J］. Br J Haematol, 2014,166（6）:842⁃848. doi: 10. 1111/bjh.12973.
［32］	Sanchorawala V, Shelton AC, Lo S, et al. Pomalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 1 and 2 trial［J］. Blood, 2016,128（8）:1059⁃1062. doi: 10.1182/blood⁃2016⁃04⁃710822.
［33］	Palladini G, Milani P, Foli A, et al. A phase 2 trial of pomalidomide and dexamethasone rescue treatment in patients with AL amyloidosis［J］. Blood, 2017,129（15）:2120⁃2123. doi: 10.1182/blood⁃2016⁃12⁃756528.
［34］	Cohen AD, Scott EC, Liedtke M, et al. A phase I dose⁃escalation study of Carfilzomib in patients with previously⁃treated systemic light⁃chain （al） amyloidosis［J］. Blood, 2014,124（21）:4741.
［35］	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［J］. Blood, 2017,130（5）:597⁃605. doi: 10.1182/blood⁃2017⁃03⁃771220.
［36］	Khouri J, Kin A, Thapa B, et al. Daratumumab proves safe and highly effective in AL amyloidosis［J］. Br J Haematol, 2019,185（2）:342⁃344. doi: 10.1111/bjh.15455.
［37］	Kaufman GP, Schrier SL, Lafayette RA, et al. Daratumumab yields rapid and deep hematologic responses in patients with heavily pretreated AL amyloidosis［J］. Blood, 2017,130（7）:900⁃902. doi: 10.1182/blood⁃2017⁃01⁃763599.
［38］	Sanchorawala V, Sarosiek S, Sloan JM, et al. Safety and tolerability of Daratumumab in patients with relapsed light chain （al） amyloidosis: preliminary results of a phaseⅡ study［J］. Blood, 2017,130（Suppl 1）:507.
［39］	Gran C, Gahrton G, Alici E, et al. Case report: treatment of light⁃chain amyloidosis with daratumumab monotherapy in two patients［J］. Eur J Haematol, 2018,100（4）:386⁃388. doi: 10. 1111/ejh.13008.
［40］	Abeykoon JP, Zanwar S, Dispenzieri A, et al. Daratumumab⁃based therapy in patients with heavily⁃pretreated AL amyloidosis［J］. Leukemia, 2019,33（2）:531⁃536. doi: 10.1038/s41375⁃018⁃0262⁃2.
［41］	Leung N, Thomé SD, Dispenzieri A. Venetoclax induced a complete response in a patient with immunoglobulin light chain amyloidosis plateaued on cyclophosphamide, bortezomib and dexamethasone［J］. Haematologica, 2018,103（3）:e135⁃e137. doi: 10.3324/haematol.2017.183749.
［42］	Palladini G, Merlini G. What is new in diagnosis and management of light chain amyloidosis?［J］. Blood, 2016,128（2）:159⁃168. doi: 10.1182/blood⁃2016⁃01⁃629790.
［43］	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］. J Clin Oncol, 2016,34（10）:1097⁃1103. doi: 10.1200/JCO.2015.63.6530.
［44］	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［J］. Amyloid, 2017,24（sup1）:58⁃59. doi: 10.1080/13506129.2017.1292900.
［45］	Richards DB, Cookson LM, Berges AC, et al. Therapeutic clearance of amyloid by antibodies to serum amyloid P component［J］. N Engl J Med, 2015,373（12）:1106⁃1114. doi: 10.1056/NEJMoa1504942.
［46］	Richards DB, Cookson LM, Barton SV, et al. Repeat doses of antibody to serum amyloid P component clear amyloid deposits in patients with systemic amyloidosis［J］. Sci Transl Med, 2018,10（422）. doi: 10.1126/scitranslmed.aan3128.

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系统性免疫球蛋白轻链型淀粉样变性的治疗进展

Treatment of systemic immunoglobulin light chain amyloidosis

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