A phase II trial of cyclophosphamide, lenalidomide and dexamethasone in previously treated patients with AL amyloidosis

被引：65

作者：

Palladini, Giovanni ^{[1
,2
]}

Russo, Paola ^{[3
,4
]}

Milani, Paolo ^{[1
,2
]}

Foli, Andrea ^{[1
,2
]}

Lavatelli, Francesca ^{[1
,2
]}

Nuvolone, Mario ^{[1
,2
]}

Perlini, Stefano ^{[1
,2
,5
]}

Merlini, Giampaolo ^{[1
,2
]}

机构：

[1] Fdn Ist Ricovero & Cura Carattere Sci IRCCS Polic, Amyloidosis Res & Treatment Ctr, Pavia, Italy

[2] Univ Pavia, Dept Mol Med, I-27100 Pavia, Italy

[3] Melegnano Hosp, Transfus Med Serv, Vizzolo Predabissi, Italy

[4] Univ Pavia, Dept Comp Engn & Syst Sci, I-27100 Pavia, Italy

[5] Univ Pavia, I-27100 Pavia, Italy

来源：

HAEMATOLOGICA | 2013年 / 98卷 / 03期

关键词：

STEM-CELL TRANSPLANTATION; LIGHT-CHAIN AMYLOIDOSIS; HIGH-DOSE MELPHALAN; MULTIPLE-MYELOMA; COMBINATION; SURVIVAL; SERUM;

D O I：

10.3324/haematol.2012.073593

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Immune-Modulatory drugs are active in immunoglobulin light-chain amyloidosis and the addition of alkylating agents can potentiate their action. In this phase II prospective trial we used cyclophosphamide, lenalidomide and dexamethasone in the treatment of 21 patients who were refractory (n=13, 62%) or relapsed (n=8, 38%) after prior treatment including rnelphalan in all cases, bortezomib in 4 and thalidomide in 6. Median number of cycles administered was 4 (range 2-9 cycles). Severe adverse events were observed in 57% of patients, most common being neutropenia (29%). The hematologic response rate was 62%, with one complete response and 5 very good partial responses. Overall median survival was three years. The achievement of CR/VGPR was associated with a significant survival advantage. The combination of cyclophosphamide, lenalidomide and dexamethasone is an effective treatment for relapsed/refractory AL amyloidosis, and good quality hematologic response should be the aim of treatment in this setting. (clinicaltrials.gov identifier: NCT00607581)

引用

页码：433 / 436

页数：4

共 24 条

[1] Electron and immuno-electron microscopy of abdominal fat identifies and characterizes amyloid fibrils in suspected cardiac amyloidosis [J].

Arbustini, E ;

Verga, L ;

Concardi, M ;

Palladini, G ;

Obici, L ;

Merlini, G .

AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS, 2002, 9 (02) :108-114

[2] Lenalidomide Maintenance after Stem-Cell Transplantation for Multiple Myeloma [J].

Attal, Michel ;

Lauwers-Cances, Valerie ;

Marit, Gerald ;

Caillot, Denis ;

Moreau, Philippe ;

Facon, Thierry ;

Stoppa, Anne Marie ;

Hulin, Cyrille ;

Benboubker, Lofti ;

Garderet, Laurent ;

Decaux, Olivier ;

Leyvraz, Serge ;

Vekemans, Marie-Christiane ;

Voillat, Laurent ;

Michallet, Mauricette ;

Pegourie, Brigitte ;

Dumontet, Charles ;

Roussel, Murielle ;

Leleu, Xavier ;

Mathiot, Claire ;

Payen, Catherine ;

Avet-Loiseau, Herve ;

Harousseau, Jean-Luc .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (19) :1782-1791

[3] Consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain amyloidosis [J].

Comenzo, R. L. ;

Reece, D. ;

Palladini, G. ;

Seldin, D. ;

Sanchorawala, V. ;

Landau, H. ;

Falk, R. ;

Wells, K. ;

Solomon, A. ;

Wechalekar, A. ;

Zonder, J. ;

Dispenzieri, A. ;

Gertz, M. ;

Streicher, H. ;

Skinner, M. ;

Kyle, R. A. ;

Merlini, G. .

LEUKEMIA, 2012, 26 (11) :2317-2325

[4] The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis [J].

Dispenzieri, Angela ;

Lacy, Martha Q. ;

Zeldenrust, Steven R. ;

Hayman, Suzanne R. ;

Kumar, Shaji K. ;

Geyer, Susan M. ;

Lust, John A. ;

Allred, Jacob B. ;

Witzig, Thomas E. ;

Rajkumar, S. Vincent ;

Greipp, Philip R. ;

Russell, Stephen J. ;

Kabat, Brian ;

Gertz, Morie A. .

BLOOD, 2007, 109 (02) :465-470

[5] Discordance between serum cardiac biomarker and immunoglobulin-free light-chain response in patients with immunoglobulin light-chain amyloidosis treated with immune modulatory drugs [J].

Dispenzieri, Angela ;

Dingli, David ;

Kumar, Shaji K. ;

Rajkumar, S. Vincent ;

Lacy, Martha Q. ;

Hayman, Suzanne ;

Buadi, Frances ;

Zeldenrust, Stephen ;

Leung, Nelson ;

Detweiler-Short, Kristen ;

Lust, John A. ;

Russell, Stephen J. ;

Kyle, Robert A. ;

Gertz, Morie A. .

AMERICAN JOURNAL OF HEMATOLOGY, 2010, 85 (10) :757-759

[6]

Gertz MA, 2010, AMYLOID, V17, P48

[7] High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis [J].

Jaccard, Arnaud ;

Moreau, Philippe ;

Leblond, Veronique ;

Leleu, Xavier ;

Benboubker, Lotfi ;

Hermine, Olivier ;

Recher, Christian ;

Asli, Bouchra ;

Lioure, Bruno ;

Royer, Bruno ;

Jardin, Fabrice ;

Bridoux, Frank ;

Grosbois, Bernard ;

Jaubert, Jerome ;

Piette, Jean-Charles ;

Ronco, Pierre ;

Quet, Fabrice ;

Cogne, Michel ;

Fermand, Jean-Paul .

NEW ENGLAND JOURNAL OF MEDICINE, 2007, 357 (11) :1083-1093

[8] A phase 1/2 study of lenalidomide with low-dose oral cyclophosphamide and low-dose dexamethasone (RdC) in AL amyloidosis [J].

Kastritis, Efstathios ;

Terpos, Evangelos ;

Roussou, Maria ;

Gavriatopoulou, Maria ;

Pamboukas, Constantinos ;

Boletis, Ioannis ;

Marinaki, Smaragda ;

Apostolou, Theofanis ;

Nikitas, Nikitas ;

Gkortzolidis, Georgios ;

Michalis, Eurydiki ;

Delimpasi, Sossana ;

Dimopoulos, Meletios A. .

BLOOD, 2012, 119 (23) :5384-5390

[9] Lenalidomide, cyclophosphamide, and dexamethasone (CRd) for light-chain amyloidosis: long-term results from a phase 2 trial [J].

Kumar, Shaji K. ;

Hayman, Suzanne R. ;

Buadi, Francis K. ;

Roy, Vivek ;

Lacy, Martha Q. ;

Gertz, Morie A. ;

Allred, Jacob ;

Laumann, Kristina M. ;

Bergsagel, Leif P. ;

Dingli, David ;

Mikhael, Joseph R. ;

Reeder, Craig B. ;

Stewart, A. Keith ;

Zeldenrust, Steven R. ;

Greipp, Philip R. ;

Lust, John A. ;

Fonseca, Rafael ;

Russell, Stephen J. ;

Rajkumar, S. Vincent ;

Dispenzieri, Angela .

BLOOD, 2012, 119 (21) :4860-4867

[10] Lenalidomide after Stem-Cell Transplantation for Multiple Myeloma [J].

McCarthy, Philip L. ;

Owzar, Kouros ;

Hofmeister, Craig C. ;

Hurd, David D. ;

Hassoun, Hani ;

Richardson, Paul G. ;

Giralt, Sergio ;

Stadtmauer, Edward A. ;

Weisdorf, Daniel J. ;

Vij, Ravi ;

Moreb, Jan S. ;

Callander, Natalie Scott ;

Van Besien, Koen ;

Gentile, Teresa ;

Isola, Luis ;

Maziarz, Richard T. ;

Gabriel, Don A. ;

Bashey, Asad ;

Landau, Heather ;

Martin, Thomas ;

Qazilbash, Muzaffar H. ;

Levitan, Denise ;

McClune, Brian ;

Schlossman, Robert ;

Hars, Vera ;

Postiglione, John ;

Jiang, Chen ;

Bennett, Elizabeth ;

Barry, Susan ;

Bressler, Linda ;

Kelly, Michael ;

Seiler, Michele ;

Rosenbaum, Cara ;

Hari, Parameswaran ;

Pasquini, Marcelo C. ;

Horowitz, Mary M. ;

Shea, Thomas C. ;

Devine, Steven M. ;

Anderson, Kenneth C. ;

Linker, Charles .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (19) :1770-1781

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